• ERβ
• Esophageal cancer
• gene expression
• meta-analysis
• systematic review

• Humans
• Adenocarcinoma/pathology
• Adenocarcinoma/metabolism
• Biomarkers, Tumor/metabolism
• Carcinoma, Squamous Cell/pathology
• Carcinoma, Squamous Cell/metabolism
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/metabolism
• Estrogen Receptor beta/metabolism
• Odds Ratio

• SULT2B1
• autosomal recessive ichthyosis
• cholesterol sulfotransferase
• colon cancer
• polymorphism
• pregnenolone sulfotransferase

• ESR2
• bioinformatic
• cancer
• gene expression
• survival
• transcriptomic

• Humans
• Neoplasms/genetics
• Gene Expression Regulation, Neoplastic
• Estrogen Receptor beta/genetics
• Estrogen Receptor beta/metabolism
• Transcriptome
• Gene Expression Profiling/methods
• Gene Regulatory Networks
• Epithelial-Mesenchymal Transition/genetics
• Prognosis
• RNA, Messenger/genetics
• RNA, Messenger/metabolism

• 2021/43/D/NZ5/02295 National Science Center

• Clinicopathological characteristics
• Gastric cardia adenocarcinoma
• Gender
• Prognosis

• Humans
• Male
• Female
• Adolescent
• Young Adult
• Adult
• Middle Aged
• Aged
• Aged, 80 and over
• Cardia/pathology
• Stomach Neoplasms/pathology
• Prognosis
• Adenocarcinoma/pathology
• Esophageal Neoplasms/pathology

• U1804262 National Natural Science Foundation of China
• 20200715 Projects of Central Government Guides for Local Science and Technology Development

• esophageal cancer
• incidence
• mortality
• projection

Esophageal cancer (EC), an aggressive and poorly understood disease, is one of the top causes of cancer-related fatalities. GLOBOCAN 2020 reports that there are 544,076 deaths and 604,100 new cases expected worldwide. Even though there are various advancements in treatment procedures, this cancer has been reported as one of the most difficult cancers to cure, and to increase patient survival; treatment targets still need to be established. Nuclear receptors (NRs) are a type of transcription factor, which has a key role in several biological processes such as reproduction, development, cellular differentiation, stress response, immunity, metabolism, lipids, and drugs, and are essential regulators of several diseases, including cancer. Numerous studies have demonstrated the importance of NRs in tumor immunology and proved the well-known roles of multiple NRs in modulating proliferation, differentiation, and apoptosis. There are surplus of studies conducted on NRs and their implications in EC, but only a few studies have demonstrated the diagnostic and prognostic potential of NRs. Therefore, there is still a paucity of the role of NRs and different ways to target them in EC cells to stop them from spreading malignancy. This review emphasizes the significance of NRs in EC by discussing their diverse agonists as well as antagonists and their response to tumor progression. Additionally, we emphasize NRs’ potential to serve as a novel therapeutic target and their capacity to treat and prevent EC.

• agonists
• antagonists
• biomarkers
• esophageal cancer
• nuclear receptors
• treatment

• Cell Differentiation
• Esophageal Neoplasms
• Humans
• Lipids
• Receptors, Cytoplasmic and Nuclear
• Transcription Factors

Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival.

To investigate the clinical features and survival factors in Chinese patients with PMME.

The clinicopathological findings of ten cases with PMME treated at Henan Provincial People’s Hospital were summarized. Moreover, the English- and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival.

A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients (55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients (36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis (LNM) was 51.2% (107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the pT stage [P < 0.001, odds ratio (OR): 2.47, 95% confidence interval (CI): 1.72-3.56] and larger tumor size (P = 0.006, OR: 1.21, 95%CI: 1.05-1.38). The median overall survival (OS) was 11.0 mo (range: 1-204 mo). The multivariate Cox analysis showed both the pT stage [P = 0.005, hazard ratio (HR): 1.70, 95%CI: 1.17-2.47] and LNM (P = 0.009, HR: 1.78, 95%CI: 1.15-2.74) were independent prognostic factors for OS. The median disease-free survival (DFS) was 5.3 mo (range: 0.8-114.1 mo). The multivariate analysis indicated that only the advanced pT stage (P = 0.02, HR: 1.93, 95%CI: 1.09-3.42) was a significant independent indicator of poor RFS in patients with PMME.

The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and pT stage are independent prognosis factors for OS, and the pT stage is the prognosis factor for DFS in patients with PMME.

• Primary malignant melanoma of the esophagus
• Clinicopathological characteristics
• Treatment
• Recurrence
• Survival

• G protein-coupled receptors
• colorectal cancer
• drug discovery
• esophageal cancer
• gastric cancer

• Animals
• Estrogens/metabolism
• Gastrointestinal Neoplasms/metabolism
• Humans
• Receptors, Angiotensin/metabolism
• Receptors, G-Protein-Coupled/chemistry
• Receptors, G-Protein-Coupled/metabolism
• Signal Transduction
• Sphingosine-1-Phosphate Receptors/metabolism

• 81570502 National Natural Science Foundation of China
• ZYJC18037 the 1.3.5 Project for Disciplines of Excellence,West China Hospital, Sichuan University

The aim of the present study was to investigate the survival and prognostic factors of patients who were with advanced esophageal squamous cell carcinoma (ESCC) and developed an esophageal fistula. The data from 221 patients with advanced ESCC developed esophageal fistula from January 2008 to December 2017 at the Harbin Medical University Cancer Hospital was retrospectively analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by the Cox proportional hazard models. The median survival time after a diagnosis of the esophageal fistula was calculated using the Kaplan–Meier method. We found that the pathogens infected by patients are common bacteria in nosocomial infection. Besides, the incidence rate of esophagomediastinal fistula was the highest (54.2%) in the lower third of the esophagus. Kaplan–Meier analysis revealed a median survival time of 11.00 months and a median post-fistula survival time of 3.63 months in patients who developed esophageal fistula in advanced esophageal cancer. In the univariate analysis, gender, therapies for ESCC before the development of fistula, type of esophageal fistula, treatment of esophageal fistula and hemoglobin (Hb) level were the factors with significant prognostic value. Gender, type of esophageal fistula and Hb level were identified as independent prognostic factors in further multivariate analysis. In summary, our study demonstrated that several factors are significantly related to patients with esophageal fistula and should be concerned about in clinical practice.

• ESCC
• esophageal fistula
• esophagomediastinal fistula
• esophagorespiratory fistula
• prognostic factor
• survival

• EC109 cell
• endoplasmic reticulum stress
• esophageal cancer
• estradiol
• gender difference

• Animals
• Apoptosis
• Butylamines/pharmacology
• Cell Movement
• Cell Proliferation
• Endoplasmic Reticulum Stress
• Esophageal Neoplasms/etiology
• Esophageal Neoplasms/metabolism
• Esophageal Neoplasms/pathology
• Esophageal Squamous Cell Carcinoma/etiology
• Esophageal Squamous Cell Carcinoma/metabolism
• Esophageal Squamous Cell Carcinoma/pathology
• Estradiol/pharmacology
• Estrogens/pharmacology
• Female
• Humans
• Mice
• Mice, Nude
• Prognosis
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays

• 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

• China
• ESCC
• South Africa
• adenocarcinoma
• alcohol
• diet
• esophageal squamous cell carcinoma
• smoking

• Esophageal squamous cell carcinoma
• Estradiol
• Estrogen receptor
• Female
• Immunohistochemistry
• Survival

Renal cell carcinoma (RCC) is an adult malignancy with 2:1 men-to-women ratio, which implies the possible role of sex hormones in RCC carcinogenesis. One of the predominant sex hormones in women before menopause, 17-β-estradiol (or E2), may regulate RCC growth by cellular mechanisms that are still not fully understood.

The expression levels of E2 receptors (ER1 and ER2) were determined in different RCC cell lines. The DNA damage response induced by E2 was determined by a DNA double-strand break marker γH2AX. To study the possible effect of E2 on oxidative stress response, RCC cells were stained with 2,7-dichlorofluorescein diacetate and analyzed by flow cytometry. Upregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) ser40 phosphorylation in response to oxidative stress was detected by immunoblotting. Finally, annexin V/propidium iodide (PI) double staining assay was used to determine E2-induced cellular apoptosis.

Variable expression of ER1 and ER2 were found in the RCC cell lines studied (786-O, A498, and ACHN), in which ACHN and A498 showed highest and lowest ER expression, respectively. In A498 cells, E2 induced DNA double-strand breaks with positive staining of γH2AX. On the other hand, the level of reactive oxidative species were elevated in ACHN cells after E2 treatment. The E2-induced oxidative stress also induced the Ser40 phosphorylation and nuclear translocation of Nrf2. Finally, we also demonstrated that E2 induced apoptosis as revealed by annexin V/PI double staining.

In this study, we demonstrated the cellular effects of E2 on DNA repair, ROS production as well as Nrf2 activation, and apoptosis in RCC cell lines. Together these cellular alterations may contribute to the reduced viability of RCC cells following E2 treatment.

• 17-β-estradiol
• DNA damage
• Estrogen receptors
• Oxidative stress
• Renal cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world. Although multimodal and targeted therapy is now used in therapeutic procedures, the survival of patients with HNSCC has remained unchanged over the last 30 years. A number of studies have demonstrated that the increased expression of intranuclear ERβ in breast, lung and colon cancer is a favorable prognostic marker associated with higher survival rates. However, the clinical significance of sex hormone receptors in HNSCC remains unclear. The current study aimed to assess the expression of ERβ in HNSCC immunohistochemically and investigate any possible association between ERβ expression, and clinical and histopathological factors, disease recurrence and patient survival. The present study included 174 patients (165 males and 9 females) with a median age of 60.8 years (range, 39–79) with HNSCC who were primary surgically treated between January 2000 and December 2006. Immunohistochemical reactions for ERβ demonstrated that 73 patients (42%) exhibited positive ERβ expression. Distribution of ERβ status among different head and neck subsites indicated that >40% of all negative cases were located in laryngeal primaries, while incidence of other sublocalization within positive cases was similar and comparable (P=0.04). Furthermore, a correlation was observed between ERβ immunopositivity and the survival of patients, with respect to the primary tumor site. Patients with ERβ positive oropharyngeal cancer had a survival rate of 35.3% at 5-years compared with 25% for patients with negative expression. However, ERβ status was not significantly correlated with any other clinical or histopathological parameter. After an average follow-up time of 38.5 months (range, 3–60 months), 54 patients (31.1%) had succumbed to disease recurrence while 50 (28.7%) succumbed to other causes. In conclusion, ERβ positivity indicates improved survival of patients with oropharyngeal cancer. Further research is required in order to implement novel therapeutic strategies.

• estrogen receptor β
• head and neck squamous cell carcinoma
• prognosis
• recurrence
• survival

• Ca2+ signaling
• Cell proliferation
• Esophageal squamous cell carcinoma
• Estrogen receptor
• Gender difference

• Esophageal squamous cell carcinoma (ESCC)
• esophagectomy
• gender
• prognosis

• adjuvant chemotherapy
• esophageal squamous cell carcinoma
• esophagectomy
• nomogram
• prognosis

Estrogen receptors are steroid hormone receptors that modulate the expression of target genes when bound to ligand. Humans have two ligand-activated transcription factors that bind to estrogen, encoded by separate genes, estrogen receptor α (ERα) and estrogen receptor β (ERβ). In addition, the membrane localized G protein-coupled estrogen receptor 1 (GPER1) can be activated by estradiol and mediate non-genomic signaling. Many studies have described the role of estrogen receptors in human cancers. Digestive system tumors account for a large proportion of all the tumors, and the mortality is very high in many digestive system tumors, such as esophageal cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, cholangiocarcinoma and pancreatic carcinoma. This review summarizes the role of estrogen receptors in digestive system tumors, aiming at finding new routes for the rational design of targeted anticancer therapies for digestive system tumors.

• Estrogen receptor
• Esophageal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Colorectal cancer
• Cholangiocarcinoma
• Pancreatic carcinoma

AIM: To determine the effects of reproductive and menstrual factors on the survival of women with esophageal squamous cell carcinoma (ESCC).

METHODS: A total of 12041 Chinese women with ESCC were enrolled in this study, and their median age was 61 years. All patients' information was retrieved from the esophageal cancer database of Henan Key Laboratory for Esophageal Cancer Research based on the records of reproduction and menstrual history. The menopausal status was categorized as pre-, peri- and post-menopausal. Questionnaire, home interview and/or telephone were performed for survival follow-up. Cox proportional hazards regression models were used for analysis of relative risks (RRs) and 95% confidence intervals (95%CIs) to determine the effects of reproductive and menstrual factors on ESCC survival.

RESULTS: Survival analysis demonstrated that patients with increased number of pregnancy had a longer survival (RR = 1.49, 95%CI: 1.16-1.92); the prolonged survival remained in patients from the high incidence area (RR = 1.41, 95%CI: 1.03-1.86) and in patients with a negative family history (RR = 1.21, 95%CI: 1.04-1.41). Pre-menopausal patients had a longer survival than peri- and postmenopausal patients (P = 0.00); this remained in patients from the high incidence area (RR for post- vs pre-menopausal, 0.73, 95%CI: 0.62-0.86) and in patients with a negative family history (RR = 0.70, 95%CI: 0.58-0.85).

CONCLUSION: Increasing number of pregnancy and premenopausal status may be favorable factors for ESCC survival in Chinese women with ESCC.

• Esophageal squamous cell carcinoma
• Reproductive
• Menopausal status
• Women
• Survival

• esophageal adenocarcinoma
• estrogen
• incidence
• sex disparity

• Alleles
• Asian People/genetics
• Carcinoma, Squamous Cell/genetics
• Case-Control Studies
• Esophageal Neoplasms/genetics
• Esophageal Squamous Cell Carcinoma
• Female
• Genetic Loci
• Genetic Predisposition to Disease
• Genome-Wide Association Study/methods
• Genotype
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk

• R37 CA70837 NCI NIH HHS
• R01 CA80205 NCI NIH HHS
• R01 CA082729 NCI NIH HHS
• ZIA CP000150-05 Intramural NIH HHS
• R01 CA144034 NCI NIH HHS
• UM1 CA173640 NCI NIH HHS
• HHSN261200800001C NCI NIH HHS
• R35 CA053890 NCI NIH HHS
• R01 CA055069 NCI NIH HHS
• HHSN261200477001C NCI NIH HHS
• N02CP11010 NCI NIH HHS
• HHSN261200800001E NCI NIH HHS
• UM1 CA182876 NCI NIH HHS
• R01 CA82729 NCI NIH HHS
• R01 CA080205 NCI NIH HHS
• UM1 CA182910 NCI NIH HHS
• ZIA CP000112-9 Intramural NIH HHS

• Esophageal cancer
• MET or MNNG HOS Transforming gene (c-Met)
• insulin-like growth factor axis (IGF axis)
• octamer-binding transcription factor 4 (OCT4)
• oestrogen receptors (ER)
• sex determining region Y-box 2 (SOX2)

• Aged
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/pathology
• Estrogen Receptor alpha/biosynthesis
• Estrogen Receptor alpha/genetics
• Estrogen Receptor beta/biosynthesis
• Estrogen Receptor beta/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Grading
• Prognosis

Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.

Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.

To the best of our knowledge our study is the first to use a cancer disease model as the framework to identify hormone responsive genes. Although we used ESCC as the disease model and estrogen as the hormone, the methodology can be extended analogously to other diseases as the model and other hormones. We believe that our results provide useful information for those interested in genes responsive to hormones and in the design of hormone-based therapies.