Materiały źródłowe

• #1 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/14428

  Esophageal cancer is a serious malignancy with high mortality. The two common distinctive pathologic subtypes of esophageal cancer are squamous cell carcinoma and adenocarcinoma. These differ with regards to etiology, ethnic distribution, pathogenesis, and location in the esophagus. […] Esophageal cancer represents 1% of all new cancer cases in the United States. It is an aggressive cancer with a high mortality and an average 5-year survival of 18.4%. […] Both of these are distinct entities with some overlap, with regards to epidemiologic distribution, risk factors, pathogenesis, and clinical and prognostic relevance. […] The decrease in ESCC is probably due to decrease in alcohol and tobacco abuse, while the increase in EAC is linked to increase in obesity and GERD. […] ESCC arise from the squamous lining of the esophagus through progression of premalignant precursor lesions that occur in the presence of risk factors that cause chronic irritation and inflammation.

• #2 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://www.wjgnet.com/1948-5204/full/v6/i5/112.htm

  Esophageal cancer is considered a serious malignancy with respect to prognosis and mortality rate. […] The two most common histological types of esophageal carcinoma include SCC and adenocarcinoma. Less than 1% to 2% of all esophageal cancers are sarcomas or small cell carcinomas. […] Major risk factors include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption may have a synergistic effect and increase the relative risk. […] The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant change. […] Adenocarcinoma of the esophagus occurs in the distal esophagus approximately three-fourths of the time and has a distinct link to gastroesophageal reflux disease (GERD).

• #3 Esophageal Cancer: An Updated Surveillance Epidemiology and End Results Database Analysis | Then | World Journal of Oncology

  https://www.wjon.org/index.php/wjon/article/view/1254/979

  Esophageal cancer is a type of malignancy characterized by its high mortality rate, poor prognosis at the time of diagnosis and significant variations in incidence, mortality, and histopathology based on geographic region. This disease is the sixth cause of cancer-related deaths and the eighth most common cancer worldwide with a 5-year survival rate of less than 25%. An estimated 17,650 cases of esophageal cancer will be diagnosed each year in the USA, from which 16,080 deaths are expected. Squamous cell carcinoma and adenocarcinoma represent the vast majority of esophageal cancers. The most common type of esophageal cancer is squamous cell carcinoma, but esophageal carcinoma is in epidemiological transition, with a dramatic increase in the incidence of esophageal adenocarcinoma (EAC) during the last 40 years.

• #4 Esophageal Cancer: An Updated Surveillance Epidemiology and End Results Database Analysis | Then | World Journal of Oncology

  https://www.wjon.org/index.php/wjon/article/view/1254/979

  Esophageal cancer is a type of malignancy characterized by its high mortality rate, poor prognosis at the time of diagnosis and significant variations in incidence, mortality, and histopathology based on geographic region. This disease is the sixth cause of cancer-related deaths and the eighth most common cancer worldwide with a 5-year survival rate of less than 25%. An estimated 17,650 cases of esophageal cancer will be diagnosed each year in the USA, from which 16,080 deaths are expected. Squamous cell carcinoma and adenocarcinoma represent the vast majority of esophageal cancers. The most common type of esophageal cancer is squamous cell carcinoma, but esophageal carcinoma is in epidemiological transition, with a dramatic increase in the incidence of esophageal adenocarcinoma (EAC) during the last 40 years.

• #5 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://www.wjgnet.com/1948-5204/full/v6/i5/112.htm

  Esophageal cancer is considered a serious malignancy with respect to prognosis and mortality rate. […] The two most common histological types of esophageal carcinoma include SCC and adenocarcinoma. Less than 1% to 2% of all esophageal cancers are sarcomas or small cell carcinomas. […] Major risk factors include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption may have a synergistic effect and increase the relative risk. […] The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant change. […] Adenocarcinoma of the esophagus occurs in the distal esophagus approximately three-fourths of the time and has a distinct link to gastroesophageal reflux disease (GERD).

• #6 Types of Esophageal Cancer | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/esophageal/types-esophageal

  Most esophageal cancers can be classified as one of two types: adenocarcinoma or squamous cell carcinoma. A third type of esophageal cancer, called small cell carcinoma, is very rare. […] Adenocarcinoma is the most common form of esophageal cancer in the United States, making up more than half of all new cases. It starts out in glandular cells, which are not normally present in the lining of the esophagus. These cells can grow there due to a condition called Barretts esophagus, which increases a persons chance of developing esophageal cancer. […] Doctors say the rise may be due to an increase in the number of people with gastroesophageal reflux disease (GERD), a condition in which contents from the stomach, such as acid and bile, move up into the esophagus repeatedly, causing chronic inflammation.

• #7 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/14428

  Esophageal cancer is a serious malignancy with high mortality. The two common distinctive pathologic subtypes of esophageal cancer are squamous cell carcinoma and adenocarcinoma. These differ with regards to etiology, ethnic distribution, pathogenesis, and location in the esophagus. […] Esophageal cancer represents 1% of all new cancer cases in the United States. It is an aggressive cancer with a high mortality and an average 5-year survival of 18.4%. […] Both of these are distinct entities with some overlap, with regards to epidemiologic distribution, risk factors, pathogenesis, and clinical and prognostic relevance. […] The decrease in ESCC is probably due to decrease in alcohol and tobacco abuse, while the increase in EAC is linked to increase in obesity and GERD. […] ESCC arise from the squamous lining of the esophagus through progression of premalignant precursor lesions that occur in the presence of risk factors that cause chronic irritation and inflammation.

• #8 Esophageal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459267/

  Esophageal cancer is classified into 2 main types based on histologic features: squamous cell carcinoma and adenocarcinoma. In recent decades, the incidence of esophageal squamous cell carcinoma has decreased. In contrast, esophageal adenocarcinoma has risen significantly in the United States, particularly in the distal esophagus and gastroesophageal junction, mainly due to the prevalence of Barrett’s esophagus. […] Risk factors for esophageal squamous cell carcinoma include smoking, alcohol consumption, and a diet low in fruits and vegetables. In contrast, esophageal adenocarcinoma high-risk factors include Barrett esophagus, smoking, high body mass index, and gastroesophageal reflux disease. […] The pathophysiology of esophageal SCC consists of a complex interaction between genetic, environmental, and lifestyle factors. Chronic irritation and inflammation caused by smoking, alcohol consumption, hot beverages, and poor nutrition can damage the esophageal mucosa. This chronic inflammation, along with exposure to carcinogens, can lead to genetic alterations, such as mutations in tumor suppressor genes (eg, p53) and oncogenes (eg, cyclin D1), disrupting normal cell cycle regulation and promoting uncontrolled cell growth.

• #9 Esophageal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459267/

  Esophageal cancer is classified into 2 main types based on histologic features: squamous cell carcinoma and adenocarcinoma. In recent decades, the incidence of esophageal squamous cell carcinoma has decreased. In contrast, esophageal adenocarcinoma has risen significantly in the United States, particularly in the distal esophagus and gastroesophageal junction, mainly due to the prevalence of Barrett’s esophagus. […] Risk factors for esophageal squamous cell carcinoma include smoking, alcohol consumption, and a diet low in fruits and vegetables. In contrast, esophageal adenocarcinoma high-risk factors include Barrett esophagus, smoking, high body mass index, and gastroesophageal reflux disease. […] The pathophysiology of esophageal SCC consists of a complex interaction between genetic, environmental, and lifestyle factors. Chronic irritation and inflammation caused by smoking, alcohol consumption, hot beverages, and poor nutrition can damage the esophageal mucosa. This chronic inflammation, along with exposure to carcinogens, can lead to genetic alterations, such as mutations in tumor suppressor genes (eg, p53) and oncogenes (eg, cyclin D1), disrupting normal cell cycle regulation and promoting uncontrolled cell growth.

• #10 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  SCC is the most common type of esophageal cancer worldwide. The overall incidence increases with age, reaching a peak in the seventh decade. SCC occurs equally as often in the middle and lower esophagus, with an incidence that is three times higher in blacks in comparison to whites. […] Major risk factors include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption may have a synergistic effect and increase the relative risk. The relative risk in men who used both heavy tobacco and alcohol was 35.4 in white males and 149.2 in black males compared to men of the same race and region who were non-smokers or drinkers. […] The mechanism of how tobacco and alcohol in combination lead to increased risk of esophageal cancer has been extensively studied. Alcohol can damage the cellular DNA by decreasing metabolic activity within the cell and therefore reduce detoxification function while promoting oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the hazardous carcinogens within tobacco are able to penetrate the esophageal epithelium easier.

• #11 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  Major risk factors for SCC include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption can have a synergistic effect. […] Alcohol damages the cellular DNA by decreasing metabolic activity within the cell and therefore inhibits detoxification and promotes oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the carcinogens within tobacco are able to penetrate the esophageal epithelium more easily. […] The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant transformation. […] Adenocarcinoma of the esophagus most commonly occurs in the distal esophagus and has a distinct relationship to GERD. Untreated GERD can progress to Barrett esophagus (BE), in which the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #12 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  SCC is the most common type of esophageal cancer worldwide. The overall incidence increases with age, reaching a peak in the seventh decade. SCC occurs equally as often in the middle and lower esophagus, with an incidence that is three times higher in blacks in comparison to whites. […] Major risk factors include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption may have a synergistic effect and increase the relative risk. The relative risk in men who used both heavy tobacco and alcohol was 35.4 in white males and 149.2 in black males compared to men of the same race and region who were non-smokers or drinkers. […] The mechanism of how tobacco and alcohol in combination lead to increased risk of esophageal cancer has been extensively studied. Alcohol can damage the cellular DNA by decreasing metabolic activity within the cell and therefore reduce detoxification function while promoting oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the hazardous carcinogens within tobacco are able to penetrate the esophageal epithelium easier.

• #13 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  Major risk factors for SCC include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption can have a synergistic effect. […] Alcohol damages the cellular DNA by decreasing metabolic activity within the cell and therefore inhibits detoxification and promotes oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the carcinogens within tobacco are able to penetrate the esophageal epithelium more easily. […] The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant transformation. […] Adenocarcinoma of the esophagus most commonly occurs in the distal esophagus and has a distinct relationship to GERD. Untreated GERD can progress to Barrett esophagus (BE), in which the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #14 Pathogenesis of Esophageal Cancer | Oncohema Key

  https://oncohemakey.com/pathogenesis-of-esophageal-cancer/

  The acetaldehyde generated by alcohol dehydrogenase has been shown to be carcinogenic in squamous cell carcinoma of the esophagus. […] Acetaldehyde forms covalent bonds with DNA, and the resulting DNA adducts can escape cellular DNA repair mechanisms causing detrimental mutations in growth-regulating genes. […] Chemical injury from a caustic chemical, such as lye, leads to fibrosis with stricture of the esophagus in the area of injury. […] The mechanism of inactivation occurs through silencing of the gene, by promoter methylation, or silencing through genome instability/chromosome translocations.

• #15 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  Other carcinogens, such as nitrosamines found in certain salted vegetables and preserved fish, have also been implicated in SCC of the esophagus. The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant change. […] Adenocarcinoma of the esophagus occurs in the distal esophagus approximately three-fourths of the time and has a distinct link to gastroesophageal reflux disease (GERD). Untreated GERD can progress to Barretts esophagus (BE), where the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium. The chronic reflux of gastric acid and bile at the gastroesophageal junction and the subsequent damage to the esophagus has been implicated in the pathogenesis of Barrett metaplasia.

• #16 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  Major risk factors for SCC include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption can have a synergistic effect. […] Alcohol damages the cellular DNA by decreasing metabolic activity within the cell and therefore inhibits detoxification and promotes oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the carcinogens within tobacco are able to penetrate the esophageal epithelium more easily. […] The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant transformation. […] Adenocarcinoma of the esophagus most commonly occurs in the distal esophagus and has a distinct relationship to GERD. Untreated GERD can progress to Barrett esophagus (BE), in which the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #17 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/14428

  The role of human papilloma virus (HPV) in development of ESCC is not well established yet. […] Chronic esophagitis: Early studies suggested that mild to moderate chronic esophagitis was associated with family history of esophageal cancer and other risk factors of ESCC. […] Squamous dysplasia is usually asymptomatic. […] The abnormality starts from the basal layer, and based on the extent of involvement of thickness of epithelium by atypical cells, the dysplasia was traditionally graded as mild, moderate and severe. […] Increasing grades of dysplasia predict increased risk of ESCC. […] Adenocarcinoma of the esophagus is a carcinoma with glandular differentiation that arises in the setting of Barretts esophagus. The most important etiological factor for EAC is Barretts esophagus in the setting of gastro-esophageal reflux.

• #18 Pathology of Esophageal Cancer | Thoracic Key

  https://thoracickey.com/pathology-of-esophageal-cancer/

  Other conditions associated with an increased risk of esophageal cancer include achalasia, diverticulosis, Plummer-Vinson syndrome, and celiac disease. […] Chronic esophagitis is common in populations with a high incidence of esophageal carcinoma, and usually involves the middle and lower thirds of the esophagus. […] Squamous dysplasia is a precursor of esophageal squamous cell carcinoma. […] Dysplasia represents a precursor lesion rather than cancerization of overlying benign epithelium by the invasive carcinoma. […] The risk of nodal metastasis increases with depth of invasion and rises dramatically once tumors have penetrated the submucosa.

• #19 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/14428

  The role of human papilloma virus (HPV) in development of ESCC is not well established yet. […] Chronic esophagitis: Early studies suggested that mild to moderate chronic esophagitis was associated with family history of esophageal cancer and other risk factors of ESCC. […] Squamous dysplasia is usually asymptomatic. […] The abnormality starts from the basal layer, and based on the extent of involvement of thickness of epithelium by atypical cells, the dysplasia was traditionally graded as mild, moderate and severe. […] Increasing grades of dysplasia predict increased risk of ESCC. […] Adenocarcinoma of the esophagus is a carcinoma with glandular differentiation that arises in the setting of Barretts esophagus. The most important etiological factor for EAC is Barretts esophagus in the setting of gastro-esophageal reflux.

• #20 Pathology of Esophageal Cancer | Thoracic Key

  https://thoracickey.com/pathology-of-esophageal-cancer/

  Other conditions associated with an increased risk of esophageal cancer include achalasia, diverticulosis, Plummer-Vinson syndrome, and celiac disease. […] Chronic esophagitis is common in populations with a high incidence of esophageal carcinoma, and usually involves the middle and lower thirds of the esophagus. […] Squamous dysplasia is a precursor of esophageal squamous cell carcinoma. […] Dysplasia represents a precursor lesion rather than cancerization of overlying benign epithelium by the invasive carcinoma. […] The risk of nodal metastasis increases with depth of invasion and rises dramatically once tumors have penetrated the submucosa.

• #21 Risk factors and molecular mechanisms of esophageal cancer: differences between the histologic subtypes

  https://www.oaepublish.com/articles/2394-4722.153534

  The two major histologic subtypes of esophageal cancer have different risk factors as well as different molecular mechanisms. […] Commonly mutated genes of both subtypes are TP53 and PIK3CA. Recent genome-wide analysis revealed that the activation of the RAC1 pathway may contribute to EAC tumorigenesis. […] Epigenetic changes, such as DNA methylation, histone modifications, and altered expression of microRNAs, have been revealed to influence carcinogenesis and progression of both ESCC and EAC. […] Recent progress in molecular biology has revealed that several genetic and epigenetic alterations are implicated in both carcinogenesis and progression of esophageal cancer. […] Genetic alterations include a chromosomal loss or gain, loss of heterozygosity (LOH), and amplification or mutations of genes.

• #22 Risk factors and molecular mechanisms of esophageal cancer: differences between the histologic subtypes

  https://www.oaepublish.com/articles/2394-4722.153534

  It has become evident that molecular mechanisms also differ greatly between the two histologic subtypes. […] The commonly mutated genes of both subtypes are TP53 and PIK3CA. […] The transcriptional genes MYC and SOX2 are occasionally amplified. […] Amplification and LOH observed in ESCC are summarized in [Table 3]. […] The PI3K/AKT pathway is activated by amplification and overexpression of receptor tyrosine kinases (fibroblast growth factor receptor 1 and epidermal growth factor receptor), KRAS, and PIK3CA. […] The promoter hypermethylation of several tumor suppressor genes, such as APC, CDKN2A, CDH1, FHIT, RARB, Ras-association domain family 1 (RASSF1), MGMT, MLH1, and MSH2, causes decreased expression of these genes and has been known to affect carcinogenesis of ESCC. […] Genome-wide DNA hypomethylation may also contribute to tumorigenesis.

• #23 Risk factors and molecular mechanisms of esophageal cancer: differences between the histologic subtypes

  https://www.oaepublish.com/articles/2394-4722.153534

  It has become evident that molecular mechanisms also differ greatly between the two histologic subtypes. […] The commonly mutated genes of both subtypes are TP53 and PIK3CA. […] The transcriptional genes MYC and SOX2 are occasionally amplified. […] Amplification and LOH observed in ESCC are summarized in [Table 3]. […] The PI3K/AKT pathway is activated by amplification and overexpression of receptor tyrosine kinases (fibroblast growth factor receptor 1 and epidermal growth factor receptor), KRAS, and PIK3CA. […] The promoter hypermethylation of several tumor suppressor genes, such as APC, CDKN2A, CDH1, FHIT, RARB, Ras-association domain family 1 (RASSF1), MGMT, MLH1, and MSH2, causes decreased expression of these genes and has been known to affect carcinogenesis of ESCC. […] Genome-wide DNA hypomethylation may also contribute to tumorigenesis.

• #24 Risk factors and molecular mechanisms of esophageal cancer: differences between the histologic subtypes

  https://www.oaepublish.com/articles/2394-4722.153534

  Histone modifications, including acetylation, methylation, phosphorylation, and ubiquitination, regulate gene expression and are implicated in carcinogenesis. […] MicroRNAs can act as tumor promoters (onco-miR) through targeting expression of tumor suppressor genes or as tumor suppressors (ts-miR) through targeting expression of oncogenes.

• #25 Esophageal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459267/

  In contrast, the pathophysiologic mechanism of esophageal adenocarcinoma is repeated exposure of the lower esophagus to stomach acid secondary to chronic GERD, which leads to the replacement of the normal squamous epithelium with metaplastic columnar epithelium (ie, Barrett esophagus). The metaplastic epithelium may progressively undergo dysplastic changes, classified as low-grade or high-grade dysplasia, based on the degree of cellular abnormalities. High-grade dysplasia can progress to invasive adenocarcinoma, where cancer cells invade the underlying layers of the esophageal wall.

• #26 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  Other carcinogens, such as nitrosamines found in certain salted vegetables and preserved fish, have also been implicated in SCC of the esophagus. The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant change. […] Adenocarcinoma of the esophagus occurs in the distal esophagus approximately three-fourths of the time and has a distinct link to gastroesophageal reflux disease (GERD). Untreated GERD can progress to Barretts esophagus (BE), where the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium. The chronic reflux of gastric acid and bile at the gastroesophageal junction and the subsequent damage to the esophagus has been implicated in the pathogenesis of Barrett metaplasia.

• #27 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  Major risk factors for SCC include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption can have a synergistic effect. […] Alcohol damages the cellular DNA by decreasing metabolic activity within the cell and therefore inhibits detoxification and promotes oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the carcinogens within tobacco are able to penetrate the esophageal epithelium more easily. […] The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant transformation. […] Adenocarcinoma of the esophagus most commonly occurs in the distal esophagus and has a distinct relationship to GERD. Untreated GERD can progress to Barrett esophagus (BE), in which the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #28 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The risk of developing esophageal cancer is 50-100 times more likely in those patients with BE. However, a majority of patients with BE will not develop EAC, the annual risk in patients with BE has been reported as 0.12%. […] Another risk factor for EAC is obesity, specifically in those individuals with predominately abdominal centered fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines. Adipocytes in the tumor microenvironment supply energy production and support tumor growth and progression.

• #29 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  The chronic reflux of gastric acid and bile at the gastroesophageal junction and the subsequent damage to the esophagus has been implicated in the pathogenesis of Barrett metaplasia. […] The progression of Barrett metaplasia to adenocarcinoma is associated with several changes in gene structure, gene expression, and protein structure. […] Obesity is another risk factor for esophageal adenocarcinoma, specifically in individuals with central fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines.

• #30 Esophageal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Esophageal_cancer

  The long-term erosive effects of acid reflux (an extremely common condition, also known as gastroesophageal reflux disease or GERD) have been strongly linked to this type of cancer. […] Longstanding GERD can induce a change of cell type in the lower portion of the esophagus in response to erosion of its squamous lining. […] This phenomenon, known as Barrett’s esophagus, seems to appear about 20 years later in women than in men, possibly due to hormonal factors. […] At a mechanistic level, in the esophagus there is a small HOXA13 expressing compartment that is more resistant to bile and acids as the normal squamous epithelium and that is prone to both intestinal differentiation as well as oncogenic transformation. […] Following GERD this HOXA13-expressing compartment outcompetes the normal squamous compartment, leading to the intestinal aspect of the esophagus and increased propensity to the development of esophageal cancer. […] Bile reflux containing unconjugated bile acids, including deoxycholic acid and chenodeoxycholic acid, appears to contribute to esophageal adenocarcinoma carcinogenesis by inducing oxidative stress and DNA damage.

• #31 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The risk of developing esophageal cancer is 50-100 times more likely in those patients with BE. However, a majority of patients with BE will not develop EAC, the annual risk in patients with BE has been reported as 0.12%. […] Another risk factor for EAC is obesity, specifically in those individuals with predominately abdominal centered fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines. Adipocytes in the tumor microenvironment supply energy production and support tumor growth and progression.

• #32 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  The chronic reflux of gastric acid and bile at the gastroesophageal junction and the subsequent damage to the esophagus has been implicated in the pathogenesis of Barrett metaplasia. […] The progression of Barrett metaplasia to adenocarcinoma is associated with several changes in gene structure, gene expression, and protein structure. […] Obesity is another risk factor for esophageal adenocarcinoma, specifically in individuals with central fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines.

• #33 Pathogenesis of Esophageal Cancer | Encyclopedia MDPI

  https://encyclopedia.pub/entry/25063

  Obesity raises the intra-abdominal pressure and this worsens reflux and thereby predisposes the development of Barrett’s esophagus and the subsequent risk for EAC. […] There are some infectious agents that have been speculated to be implicated in the pathogenesis of esophageal cancer. Bacteria such as Helicobacter pylori and viral agents such as the Human papillomavirus types 16 and 18 may contribute to the development of esophageal cancer. […] Changes at the genome level are known to play a part in the pathogenesis of esophageal cancer. Genes that regulate the cell cycle are mutated or are over-expressed in cases of ESCC.

• #34 Esophageal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Esophageal_cancer

  The two main sub-types of the disease are esophageal squamous-cell carcinoma (often abbreviated to ESCC), which is more common in the developing world, and esophageal adenocarcinoma (EAC), which is more common in the developed world. […] Squamous-cell carcinoma arises from the epithelial cells that line the esophagus. […] Adenocarcinoma arises from glandular cells present in the lower third of the esophagus, often where they have already transformed to intestinal cell type (a condition known as Barrett’s esophagus). […] Causes of the squamous-cell type include tobacco, alcohol, very hot drinks, poor diet, and chewing betel nut. […] The most common causes of the adenocarcinoma type are smoking tobacco, obesity, and acid reflux. […] In addition, for patients with achalasia, candidiasis (overgrowth of the esophagus with the fungus candida) is the most important risk factor.

• #35 Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights

  https://www.mdpi.com/1422-0067/25/5/2978

  Esophageal cancer (EC) remains a formidable malignancy with limited treatment options and high mortality rates, necessitating the exploration of innovative therapeutic avenues. […] This review comprehensively elucidates the intricate metabolic pathways and molecular mechanisms through which metformin may exert its anti-cancer effects. Key focus areas include its impact on insulin signaling, AMP-activated protein kinase (AMPK) activation, and the mTOR pathway, which collectively contribute to its role in mitigating esophageal cancer progression. […] The pathogenesis of EAC involves reflux-induced DNA damage, especially A>C transversions, contributing to BE development as an adaptive response to squamous mucosa injury. Barrett’s mucosa, a pre-neoplastic tissue, frequently contains somatic genetic alterations, including TP53 and SMAD4 mutations, contributing to carcinogenesis.

• #36 Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights

  https://www.mdpi.com/1422-0067/25/5/2978

  The heterogeneity of EAC poses challenges for targeted therapies, and whole-genome sequencing has identified subgroups with potential therapeutic implications, such as DNA damage repair-deficient subtypes benefiting from PARP/ATR inhibitors or platinum-based chemotherapy and subgroups with a high mutational burden responding to immuno-oncology therapies. […] Metformin inhibits cancer through direct and indirect pathways, impacting multiple molecular mechanisms. The activation of AMPK plays a crucial role, inhibiting cellular proliferation and inducing G1-phase cell cycle arrest. […] Metformin also activates the multidrug resistance 1 (MDR1) gene, potentially reducing drug failure in chemotherapy. […] The inhibition of the mammalian target of rapamycin (mTOR) pathway by metformin suppresses cancer progression and angiogenesis.

• #37 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/14428

  Barretts esophagus is essentially defined as columnar metaplasia that replaces the stratified squamous epithelium of the distal esophagus, and has a predisposition to develop adenocarcinoma. […] The development of EAC appears to occur through progressive accumulation of multiple genetic abnormalities such as mutational inactivation of p16, and p53 genes, cell cycle abnormalities and aneuploidy. The molecular mechanism is complex and cannot be attributed to a single genetic event.

• #38 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/html

  Barretts esophagus is essentially defined as columnar metaplasia that replaces the stratified squamous epithelium of the distal esophagus, and has a predisposition to develop adenocarcinoma. […] The development of EAC appears to occur through progressive accumulation of multiple genetic abnormalities such as mutational inactivation of p16, and p53 genes, cell cycle abnormalities and aneuploidy. The molecular mechanism is complex and cannot be attributed to a single genetic event.

• #39 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] More recently, researchers have studied alterations in esophageal microbiota that may contribute to the development of EC. […] The presence of lipopolysaccharide (LPS) on the surface of Gram-negative bacteria activates the NF-B pathway, leading to elevated expression of IL-8, which is a significant event in the transition from a normal esophagus to BE.

• #40 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] One of the hurdles in studying the esophageal microbiome involves obtaining samples from the esophageal epithelium because this procedure is invasive and may result in complications. […] The presence of lipopolysaccharide (LPS) on the surface of Gram-negative bacteria activates the NF-B pathway, leading to elevated expression of IL-8, which is a significant event in the transition from a normal esophagus to BE.

• #41 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] More recently, researchers have studied alterations in esophageal microbiota that may contribute to the development of EC. […] The presence of lipopolysaccharide (LPS) on the surface of Gram-negative bacteria activates the NF-B pathway, leading to elevated expression of IL-8, which is a significant event in the transition from a normal esophagus to BE.

• #42 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] One of the hurdles in studying the esophageal microbiome involves obtaining samples from the esophageal epithelium because this procedure is invasive and may result in complications. […] The presence of lipopolysaccharide (LPS) on the surface of Gram-negative bacteria activates the NF-B pathway, leading to elevated expression of IL-8, which is a significant event in the transition from a normal esophagus to BE.

• #43 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  These findings support the previous study by Yang et al. which revealed a higher proportion of type II microorganisms in diseased esophagus compared to type I microorganisms. […] The presence of H. pylori can influence the microbial composition of the lower esophagus. […] The tumor tissues of these affected patients have increased production of chemokines, which contributes to a more aggressive disease course and reduced survival. […] Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #44 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  Taken together, these studies suggest that BE-induced microbiome changes in the esophagus may contribute to the development of EAC. […] The presence of H. pylori can influence the microbial composition of the lower esophagus. […] Although the precise mechanisms underlying this inverse correlation between H. pylori infection and EAC remain unclear, researchers have proposed various explanations for this phenomenon. […] These findings suggested that P. gingivalis could serve as a novel prognostic indicator for ESCC. […] Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #45 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  These findings support the previous study by Yang et al. which revealed a higher proportion of type II microorganisms in diseased esophagus compared to type I microorganisms. […] The presence of H. pylori can influence the microbial composition of the lower esophagus. […] The tumor tissues of these affected patients have increased production of chemokines, which contributes to a more aggressive disease course and reduced survival. […] Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #46 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  Taken together, these studies suggest that BE-induced microbiome changes in the esophagus may contribute to the development of EAC. […] The presence of H. pylori can influence the microbial composition of the lower esophagus. […] Although the precise mechanisms underlying this inverse correlation between H. pylori infection and EAC remain unclear, researchers have proposed various explanations for this phenomenon. […] These findings suggested that P. gingivalis could serve as a novel prognostic indicator for ESCC. […] Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #47 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  These findings support the previous study by Yang et al. which revealed a higher proportion of type II microorganisms in diseased esophagus compared to type I microorganisms. […] The presence of H. pylori can influence the microbial composition of the lower esophagus. […] The tumor tissues of these affected patients have increased production of chemokines, which contributes to a more aggressive disease course and reduced survival. […] Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #48 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  Taken together, these studies suggest that BE-induced microbiome changes in the esophagus may contribute to the development of EAC. […] The presence of H. pylori can influence the microbial composition of the lower esophagus. […] Although the precise mechanisms underlying this inverse correlation between H. pylori infection and EAC remain unclear, researchers have proposed various explanations for this phenomenon. […] These findings suggested that P. gingivalis could serve as a novel prognostic indicator for ESCC. […] Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #49

  https://link.springer.com/article/10.1007/s44178-023-00056-7

  The occurrence and development of esophageal cancer (EC) is a multi-stage process involving from inflammation to invasive cancer. […] Current studies have shown that EC is a multi-stage process that gradually develops from repeated inflammatory stimulation to precancerous lesions and then to invasive cancer. This process is very complex and involves changes in esophageal epithelial and non-epithelial cells cytogenetics in the microenvironment, and its molecular mechanisms are still being explored. […] The progression of EC from precancerous lesions to invasive carcinoma is very complex. With the development of sequencing techniques, researchers have gradually revealed some key genes and pathways affecting the occurrence and development of EC through sequencing. […] Previous studies have shown that chronic inflammation of the cellular microenvironment is a strong risk factor for digestive system tumors.

• #50 Esophageal cancer: current status and new insights fro…

  https://ppch.pl/seo/article/01.3001.0054.4523/en

  Esophageal cancer (EC) arises from a complex interplay of genetic predispositions and environmental factors. […] Chronic inflammation plays a pivotal role in the initiation and progression of EC. […] The pathophysiology of this process is not fully understood, but it is often argued that genetic factors, gut microbiota, and the presence of chronic irritation or inflammation can play a pivotal role in this complex process. […] Esophageal carcinogenesis arises from a multifaceted interplay among environmental factors, genetic predisposition, and chronic inflammation. […] In EAC, inflammation arises in close connection with gastroesophageal reflux, resulting in both tissue damage and heightened production of reactive oxygen species (ROS). […] The increased production of ROS can induce DNA damage, resulting in tumor-initiating mutations, and active signaling pathways, such as P13K/Akt, ERK1/2, and NF-κB, which are associated with cancer.

• #51

  https://link.springer.com/article/10.1007/s44178-023-00056-7

  The occurrence and development of esophageal cancer (EC) is a multi-stage process involving from inflammation to invasive cancer. […] Current studies have shown that EC is a multi-stage process that gradually develops from repeated inflammatory stimulation to precancerous lesions and then to invasive cancer. This process is very complex and involves changes in esophageal epithelial and non-epithelial cells cytogenetics in the microenvironment, and its molecular mechanisms are still being explored. […] The progression of EC from precancerous lesions to invasive carcinoma is very complex. With the development of sequencing techniques, researchers have gradually revealed some key genes and pathways affecting the occurrence and development of EC through sequencing. […] Previous studies have shown that chronic inflammation of the cellular microenvironment is a strong risk factor for digestive system tumors.

• #52

  https://link.springer.com/article/10.1007/s44178-023-00056-7

  The complex background of tumor microenvironment (TME) also plays an important role in the occurrence and development of tumors. […] Generally speaking, the occurrence of ESCC is caused by the combined effects of external carcinogenic stimulation, inflammatory response, gene mutation and immunosuppression.

• #53 Esophageal cancer: current status and new insights fro…

  https://ppch.pl/seo/article/01.3001.0054.4523/en

  Esophageal cancer (EC) arises from a complex interplay of genetic predispositions and environmental factors. […] Chronic inflammation plays a pivotal role in the initiation and progression of EC. […] The pathophysiology of this process is not fully understood, but it is often argued that genetic factors, gut microbiota, and the presence of chronic irritation or inflammation can play a pivotal role in this complex process. […] Esophageal carcinogenesis arises from a multifaceted interplay among environmental factors, genetic predisposition, and chronic inflammation. […] In EAC, inflammation arises in close connection with gastroesophageal reflux, resulting in both tissue damage and heightened production of reactive oxygen species (ROS). […] The increased production of ROS can induce DNA damage, resulting in tumor-initiating mutations, and active signaling pathways, such as P13K/Akt, ERK1/2, and NF-κB, which are associated with cancer.

• #54 Esophageal cancer: current status and new insights fro…

  https://ppch.pl/seo/article/01.3001.0054.4523/en

  In general, activation of inflammatory signaling pathways stands as a pivotal mechanism in carcinogenesis, leading to downstream activation of gene transcription and a decrease in enzymatic activity. […] Chronic inflammation plays a pivotal role in the initiation and progression of both ESCC and EAC. […] Local and systemic inflammation play pivotal roles in the development of EC. […] Inflammatory markers can be clinically useful not only in predicting the development of EC but also in prognosis. […] Chronic inflammation plays a pivotal role in the initiation and progression of both ESCC and EAC.

• #55 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Esophageal cancer (EC) is a disease often marked by aggressive growth and poor prognosis. […] The complex and dynamic interactions of the secreted cytokines, chemokines, growth factors, and their receptors mediate chronic inflammation and immunosuppressive TME favoring tumor progression, metastasis, and decreased response to therapy. […] This review highlighted the novel insights into the understanding and functional impact of deregulated cytokines and chemokines in imparting aggressive EC, stressing the nature and therapeutic consequences of the cytokine-chemokine network. […] We also discuss cytokine-chemokine oncogenic potential by contributing to the Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niche, and therapeutic resistance development.

• #56 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Recent studies have conclusively established an essential role of the tumor microenvironment (TME) in EC progression and metastasis. […] Their practical importance is in imparting an aggressive EC phenotype by contributing to Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niches, and therapeutic resistance. […] The cytokines and chemokines secreted by the immune cells mediate cancer-stromal interactions and activate several downstream effector pathways such as JAK/STAT, NF-, NOTCH to mediate various properties of cancer hallmarks. […] The activation of STAT3 by its major inducers, IL-6, and IL-6R, has been associated with poor prognosis in patients undergoing esophagectomy. […] The CC chemokine, CCL5 (also known as RANTES), is a downstream target of the NF-B pathway known to promote tumor cell proliferation, invasion, and angiogenesis by facilitating the recruitment of eosinophils, monocytes, T cells, and basophils.

• #57 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Recent studies have conclusively established an essential role of the tumor microenvironment (TME) in EC progression and metastasis. […] Their practical importance is in imparting an aggressive EC phenotype by contributing to Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niches, and therapeutic resistance. […] The cytokines and chemokines secreted by the immune cells mediate cancer-stromal interactions and activate several downstream effector pathways such as JAK/STAT, NF-, NOTCH to mediate various properties of cancer hallmarks. […] The activation of STAT3 by its major inducers, IL-6, and IL-6R, has been associated with poor prognosis in patients undergoing esophagectomy. […] The CC chemokine, CCL5 (also known as RANTES), is a downstream target of the NF-B pathway known to promote tumor cell proliferation, invasion, and angiogenesis by facilitating the recruitment of eosinophils, monocytes, T cells, and basophils.

• #58 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  EC pathogenesis is associated with the deregulation of many cytokines and chemokines. […] Pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) have been linked with EC pathogenesis. […] IL-1 is involved in promoting angiogenesis through the production of vascular endothelial growth factor (VEGF). […] The release of IL-1 from M2 macrophages associated with increased expression (phosphorylation) of both NF-B and IB suggests that IL-1 regulates EMT through the NF-B pathway. […] Several cytokines and chemokines promote EMT in EC and are associated with poor prognosis and clinical outcome. […] The IL-6/STAT3/TWIST signaling pathway inhibition is found to reverse ionizing radiation (IR)-induced EMT and radioresistance in ESCC.

• #59 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  EC pathogenesis is associated with the deregulation of many cytokines and chemokines. […] Pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) have been linked with EC pathogenesis. […] IL-1 is involved in promoting angiogenesis through the production of vascular endothelial growth factor (VEGF). […] The release of IL-1 from M2 macrophages associated with increased expression (phosphorylation) of both NF-B and IB suggests that IL-1 regulates EMT through the NF-B pathway. […] Several cytokines and chemokines promote EMT in EC and are associated with poor prognosis and clinical outcome. […] The IL-6/STAT3/TWIST signaling pathway inhibition is found to reverse ionizing radiation (IR)-induced EMT and radioresistance in ESCC.

• #60 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  The induction of IL-6 is found to increase the expression of ALDH1, a CSC marker, and TWIST, an essential EMT inducer, in a xenograft tumor model. […] The elevated expression of MMP2, MMP7, MMP9, and vimentin and the reduced expression of E-cadherin in ALDH1A1high ESCC indicates a close relationship between EMT and ALDH1A1 expression. […] The cytokine/chemokine network contributes to the aggressiveness of ESCC and correlates with primary tumor progression, lymph and distant metastasis, and patient outcome. […] The findings presented in this review reveal the potential of disrupting the interaction between tumor cells and TME components for ESCC therapy.

• #61 Pathogenesis, diagnosis, and treatment of esophageal cancer | IJN

  https://www.dovepress.com/the-significance-of-exosomes-in-pathogenesis-diagnosis-and-treatment-o-peer-reviewed-fulltext-article-IJN

  Esophageal cancer is one of the most common malignancy in China with high mortality. Understanding pathogenesis and identifying early diagnosis biomarkers can significantly improve the prognosis of patients with esophageal cancer. […] Exosomes are small vesicular structures containing a variety of components (including DNA, RNA, and proteins) mediating cell-to-cell material exchange and signal communication. […] Growing evidences have shown that exosomes and its components are involved in growth, metastasis and angiogenesis in cancer, and could also be used as diagnostic and prognostic markers. […] We summarized recent progress to elucidate the significance of exosomes in the esophageal cancer progression, microenvironment remodeling, therapeutic resistance, and immunosuppression. […] Exosomes play important roles in different stages of tumor development cascade including tumor proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), migration, microenvironment remodeling, and therapeutic resistance.

• #62 Pathogenesis, diagnosis, and treatment of esophageal cancer | IJN

  https://www.dovepress.com/the-significance-of-exosomes-in-pathogenesis-diagnosis-and-treatment-o-peer-reviewed-fulltext-article-IJN

  Esophageal cancer is one of the most common malignancy in China with high mortality. Understanding pathogenesis and identifying early diagnosis biomarkers can significantly improve the prognosis of patients with esophageal cancer. […] Exosomes are small vesicular structures containing a variety of components (including DNA, RNA, and proteins) mediating cell-to-cell material exchange and signal communication. […] Growing evidences have shown that exosomes and its components are involved in growth, metastasis and angiogenesis in cancer, and could also be used as diagnostic and prognostic markers. […] We summarized recent progress to elucidate the significance of exosomes in the esophageal cancer progression, microenvironment remodeling, therapeutic resistance, and immunosuppression. […] Exosomes play important roles in different stages of tumor development cascade including tumor proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), migration, microenvironment remodeling, and therapeutic resistance.

• #63 Pathogenesis, diagnosis, and treatment of esophageal cancer | IJN

  https://www.dovepress.com/the-significance-of-exosomes-in-pathogenesis-diagnosis-and-treatment-o-peer-reviewed-fulltext-article-IJN

  Growing evidences demonstrated that exosomes could regulate the growth and metastasis of EC through secreting biologically active components. […] Tumor-derived exosomal miR-93-5p could be transferred to EC9706 EC cells, which might inhibit the expression of p21 and Cyclin D1 through the phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway to promote tumor cell proliferation. […] Tumor-derived exosomal lncRNA ZFAS1 favored the tumorigenesis in EC cells through promoting proliferation, migration, and invasion but suppressing apoptosis by upregulating signal transducer and activator of transcription 3 (STAT3) and downregulating miR-124. […] The facts mentioned above highlight that exosomes play a significant role in growth and metastasis of EC.

• #64 Pathogenesis, diagnosis, and treatment of esophageal cancer | IJN

  https://www.dovepress.com/the-significance-of-exosomes-in-pathogenesis-diagnosis-and-treatment-o-peer-reviewed-fulltext-article-IJN

  Growing evidences demonstrated that exosomes could regulate the growth and metastasis of EC through secreting biologically active components. […] Tumor-derived exosomal miR-93-5p could be transferred to EC9706 EC cells, which might inhibit the expression of p21 and Cyclin D1 through the phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway to promote tumor cell proliferation. […] Tumor-derived exosomal lncRNA ZFAS1 favored the tumorigenesis in EC cells through promoting proliferation, migration, and invasion but suppressing apoptosis by upregulating signal transducer and activator of transcription 3 (STAT3) and downregulating miR-124. […] The facts mentioned above highlight that exosomes play a significant role in growth and metastasis of EC.

• #65 Pathogenesis, diagnosis, and treatment of esophageal cancer | IJN

  https://www.dovepress.com/the-significance-of-exosomes-in-pathogenesis-diagnosis-and-treatment-o-peer-reviewed-fulltext-article-IJN

  Emerging evidences indicate exosomal involves in EC angiogenesis. […] During EMT, epithelial cells lose polarity and acquire aggressive mesenchymal phenotype favoring tumor cells progression. […] The studies mentioned above indicate that exosomes can induce the angiogenesis and EMT by regulating various gene expression and signal transduction in EC. […] Exosomes from cancer cells, immune cells, and CAFs mediated signaling pathway play central role in tumor progression by remodeling the microenvironment. […] The above studies have shown that EC microenvironment remodeling is closely related to the regulation of various gene expression and signal transduction by exosome. […] Recent studies have shown that tumor-derived exosomes participate in the development of immunosuppressive microenvironment.

• #66 Pathogenesis, diagnosis, and treatment of esophageal cancer | IJN

  https://www.dovepress.com/the-significance-of-exosomes-in-pathogenesis-diagnosis-and-treatment-o-peer-reviewed-fulltext-article-IJN

  Emerging evidences indicate exosomal involves in EC angiogenesis. […] During EMT, epithelial cells lose polarity and acquire aggressive mesenchymal phenotype favoring tumor cells progression. […] The studies mentioned above indicate that exosomes can induce the angiogenesis and EMT by regulating various gene expression and signal transduction in EC. […] Exosomes from cancer cells, immune cells, and CAFs mediated signaling pathway play central role in tumor progression by remodeling the microenvironment. […] The above studies have shown that EC microenvironment remodeling is closely related to the regulation of various gene expression and signal transduction by exosome. […] Recent studies have shown that tumor-derived exosomes participate in the development of immunosuppressive microenvironment.

• #67 Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

  https://www.wjgnet.com/1007-9327/full/v30/i16/2195.htm

  A suppressive TIME is usually accompanied by the reduced infiltration or exhaustion of immune cells, and is correlated mainly with the presence of immunosuppressive cells and coinhibitory signals. […] T cells are the major component of infiltrated immune cells in most solid tumors, and CD8+ cytotoxic T cells (CTLs) and CD4+ T helper cells (Ths) play crucial roles in eliminating tumor cells. […] Activated T cells may express various inhibitory receptors, known as immune checkpoints, to prevent excessive immune responses, aiming to maintain an immunologic balance; however, tumor cells may exploit these checkpoints to induce coinhibitory signals in the TME and create an immunosuppressive TME, which plays a pivotal role in tumor immune escape. […] Tumor immune escape is often accompanied by a decrease in or loss of MHC molecules, which play crucial roles in the recognition and killing of tumor cells by immune cells.

• #68 Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

  https://www.wjgnet.com/1007-9327/full/v30/i16/2195.htm

  A suppressive TIME is usually accompanied by the reduced infiltration or exhaustion of immune cells, and is correlated mainly with the presence of immunosuppressive cells and coinhibitory signals. […] T cells are the major component of infiltrated immune cells in most solid tumors, and CD8+ cytotoxic T cells (CTLs) and CD4+ T helper cells (Ths) play crucial roles in eliminating tumor cells. […] Activated T cells may express various inhibitory receptors, known as immune checkpoints, to prevent excessive immune responses, aiming to maintain an immunologic balance; however, tumor cells may exploit these checkpoints to induce coinhibitory signals in the TME and create an immunosuppressive TME, which plays a pivotal role in tumor immune escape. […] Tumor immune escape is often accompanied by a decrease in or loss of MHC molecules, which play crucial roles in the recognition and killing of tumor cells by immune cells.

• #69 Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

  https://www.wjgnet.com/1007-9327/full/v30/i16/2195.htm

  A suppressive TIME is usually accompanied by the reduced infiltration or exhaustion of immune cells, and is correlated mainly with the presence of immunosuppressive cells and coinhibitory signals. […] T cells are the major component of infiltrated immune cells in most solid tumors, and CD8+ cytotoxic T cells (CTLs) and CD4+ T helper cells (Ths) play crucial roles in eliminating tumor cells. […] Activated T cells may express various inhibitory receptors, known as immune checkpoints, to prevent excessive immune responses, aiming to maintain an immunologic balance; however, tumor cells may exploit these checkpoints to induce coinhibitory signals in the TME and create an immunosuppressive TME, which plays a pivotal role in tumor immune escape. […] Tumor immune escape is often accompanied by a decrease in or loss of MHC molecules, which play crucial roles in the recognition and killing of tumor cells by immune cells.

• #70 Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

  https://www.wjgnet.com/1007-9327/full/v30/i16/2195.htm

  An immunosuppressive TME is partially generated by immunosuppressive factors secreted by tumor cells, immune cells and stromal cells, and these factors play crucial roles in tumor proliferation, angiogenesis and invasion, as well as in EC progression. […] The interplay of cytokines and signaling pathways in the TIME of EC results in the construction of a complex network, and certain key cytokines, such as TGF- and IFN-, play dual roles in tumor progression by promoting tumor growth and immune escape or exerting antitumor effects. […] Understanding the intricate interactions among these factors might provide insights into potential therapeutic targets for enhancing antitumor immunity in patients with EC.

• #71 Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

  https://www.wjgnet.com/1007-9327/full/v30/i16/2195.htm

  An immunosuppressive TME is partially generated by immunosuppressive factors secreted by tumor cells, immune cells and stromal cells, and these factors play crucial roles in tumor proliferation, angiogenesis and invasion, as well as in EC progression. […] The interplay of cytokines and signaling pathways in the TIME of EC results in the construction of a complex network, and certain key cytokines, such as TGF- and IFN-, play dual roles in tumor progression by promoting tumor growth and immune escape or exerting antitumor effects. […] Understanding the intricate interactions among these factors might provide insights into potential therapeutic targets for enhancing antitumor immunity in patients with EC.

• #72 Biomedicines | Special Issue : Esophageal Cancer — Pathogenesis and Therapeutic Strategies

  https://www.mdpi.com/journal/biomedicines/special_issues/FZA294U9F8

  Esophageal cancer; gastric cancer; neuroendocrine tumor; biomarkers; molecular epidemiology […] Targeted therapies for esophageal cancer are important personalized treatments and may improve cancer outcomes. Previous studies and the genetic profiling of esophageal cancer have lead the treatment strategy from traditional chemoradiotherapy to immunotherapy. For poor responders to palliative chemotherapy, clinical trials on immune checkpoint inhibitors, targeting programmed death-1 (PD-1), PD-ligand 1 (PD-L1), or CTLA-4, have shown promising activity. Responders to immunotherapy may enjoy sustainable effects, but there is still no reliable biomarker to predict the response. Moreover, studies on esophageal carcinogenesis are ongoing, but the exact mechanisms behind it as well as the tumor microenvironment remain unclear.

• #73 Multidisciplinary Team Identifies a Mechanism for Inhibiting Metastatic Esophageal Cancer – Advances in Oncology & Gastroenterology | NewYork-Presbyterian

  https://www.nyp.org/advances/article/multidisciplinary-team-identifies-a-mechanism-for-inhibiting-metastatic-esophageal-cancer

  Gastroenterologists, oncologists, and geneticists from NewYork-Presbyterian/Columbia have identified a genetic mechanism that could hold the key to developing treatments for metastatic esophageal squamous cell carcinoma (ESCC), a deadly form of esophageal cancer in the US and worldwide without effective treatment options. […] The findings, published in Cancer Discovery in December 2023, suggest that the CSF-1/CSF-1R axis could be an important target for the development of therapeutics for metastatic ESCC. This is the first time that CSF-1/CSF-1R has been identified as a potential mechanism for treating ESCC. […] CSF-1 creates an environment that is conducive or permissive for metastasis. If we take it out of our system, the lung metastases essentially go away, sort of like an Achilles heel, even in the face of mutant p53 still being there.

• #74 Multidisciplinary Team Identifies a Mechanism for Inhibiting Metastatic Esophageal Cancer – Advances in Oncology & Gastroenterology | NewYork-Presbyterian

  https://www.nyp.org/advances/article/multidisciplinary-team-identifies-a-mechanism-for-inhibiting-metastatic-esophageal-cancer

  Gastroenterologists, oncologists, and geneticists from NewYork-Presbyterian/Columbia have identified a genetic mechanism that could hold the key to developing treatments for metastatic esophageal squamous cell carcinoma (ESCC), a deadly form of esophageal cancer in the US and worldwide without effective treatment options. […] The findings, published in Cancer Discovery in December 2023, suggest that the CSF-1/CSF-1R axis could be an important target for the development of therapeutics for metastatic ESCC. This is the first time that CSF-1/CSF-1R has been identified as a potential mechanism for treating ESCC. […] CSF-1 creates an environment that is conducive or permissive for metastasis. If we take it out of our system, the lung metastases essentially go away, sort of like an Achilles heel, even in the face of mutant p53 still being there.

• #75 Multidisciplinary Team Identifies a Mechanism for Inhibiting Metastatic Esophageal Cancer – Advances in Oncology & Gastroenterology | NewYork-Presbyterian

  https://www.nyp.org/advances/article/multidisciplinary-team-identifies-a-mechanism-for-inhibiting-metastatic-esophageal-cancer

  The CSF-1/CSF-1R axis is a potential target for future therapies to treat metastatic ESCC. […] The paper also explores the biochemistry of how mutant p53 works to induce CSF-1, a finding that suggests mutant p53 could be used as a biomarker for upregulation of CSF-1 in metastatic ESCC. […] You can imagine combinatorial therapy where you can utilize drugs against specific targets induced by mutant p53, Dr. Rustgi says. […] The research is an important potential advance in the treatment of metastatic ESCC, but it also has implications in other cancers with common genomic properties, including head and neck squamous cell carcinoma and lung squamous cell carcinoma.

• #76 Multidisciplinary Team Identifies a Mechanism for Inhibiting Metastatic Esophageal Cancer – Advances in Oncology & Gastroenterology | NewYork-Presbyterian

  https://www.nyp.org/advances/article/multidisciplinary-team-identifies-a-mechanism-for-inhibiting-metastatic-esophageal-cancer

  The CSF-1/CSF-1R axis is a potential target for future therapies to treat metastatic ESCC. […] The paper also explores the biochemistry of how mutant p53 works to induce CSF-1, a finding that suggests mutant p53 could be used as a biomarker for upregulation of CSF-1 in metastatic ESCC. […] You can imagine combinatorial therapy where you can utilize drugs against specific targets induced by mutant p53, Dr. Rustgi says. […] The research is an important potential advance in the treatment of metastatic ESCC, but it also has implications in other cancers with common genomic properties, including head and neck squamous cell carcinoma and lung squamous cell carcinoma.

• #77 Multidisciplinary Team Identifies a Mechanism for Inhibiting Metastatic Esophageal Cancer – Advances in Oncology & Gastroenterology | NewYork-Presbyterian

  https://www.nyp.org/advances/article/multidisciplinary-team-identifies-a-mechanism-for-inhibiting-metastatic-esophageal-cancer

  The CSF-1/CSF-1R axis is a potential target for future therapies to treat metastatic ESCC. […] The paper also explores the biochemistry of how mutant p53 works to induce CSF-1, a finding that suggests mutant p53 could be used as a biomarker for upregulation of CSF-1 in metastatic ESCC. […] You can imagine combinatorial therapy where you can utilize drugs against specific targets induced by mutant p53, Dr. Rustgi says. […] The research is an important potential advance in the treatment of metastatic ESCC, but it also has implications in other cancers with common genomic properties, including head and neck squamous cell carcinoma and lung squamous cell carcinoma.

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