Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological type of esophageal cancer, predominantly constituting 90% of cases worldwide. Despite the development of multidisciplinary ...therapeutic approaches, its prognosis remains unfavorable. Recently, the development of monoclonal antibodies inhibiting programmed death 1 (PD‐1) or programmed death‐ligand 1 (PD‐L1) has led to marked therapeutic responses among multiple malignancies including ESCC. However, only a few patients achieved clinical benefits due to resistance. Therefore, precise and accurate predictive biomarkers should be identified for personalized immunotherapy in clinical settings. Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD‐L1 expression on tumors, tumor‐infiltrating lymphocytes, tumor‐associated macrophages, and myeloid‐derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.
Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD‐L1 expression on tumors, tumor‐infiltrating lymphocytes, tumor‐associated macrophages, and myeloid‐derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.
The epithelial–mesenchymal transition (EMT) plays a critical role in embryonic development. EMT is also involved in cancer progression and metastasis and it is probable that a common molecular ...mechanism is shared by these processes. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. Furthermore, the acquisition of EMT features has been associated with chemoresistance which could give rise to recurrence and metastasis after standard chemotherapeutic treatment. Thus, EMT could be closely involved in carcinogenesis, invasion, metastasis, recurrence, and chemoresistance. Research into EMT and its role in cancer pathogenesis has progressed rapidly and it is now hypothesized that novel concepts such as cancer stem cells and microRNA could be involved in EMT. However, the involvement of EMT varies greatly among cancer types, and much remains to be learned. In this review, we present recent findings regarding the involvement of EMT in cancer progression and metastasis and provide a perspective from clinical and translational viewpoints. (Cancer Sci 2009)
Increasing lines of evidence show that the malignant behavior of cancer is not exclusively attributable to cancer cells but also radically influenced by cancerous stroma activity and controlled ...through various mechanisms by the microenvironment. In addition to structural components, such as the extracellular matrix, stromal cells, such as macrophages, endothelial cells, and specifically cancer-associated fibroblasts (CAFs), have attracted substantial attention over recent decades. CAFs provide routes for aggressive carcinomas and contribute to invasion and metastasis through the biochemical alteration and regulation of cancer-related pathways. However, another facet of CAFs that has been neglected by numerous studies is that CAFs might serve as a negative regulator of cancer progression under certain circumstances. The various origins of CAFs, the diverse tissues in which they reside and their interactions with different cancer cells appear to be responsible for this inconsistency. This review summarizes the latest knowledge regarding CAF heterogeneity and offers a novel perspective and a beneficial approach for obtaining an improved understanding of CAFs.
Metagenomic studies using next-generation sequencing technologies have revealed rich human intestinal microbiome, which likely influence host immunity and health conditions including cancer. Evidence ...indicates a biological link between altered microbiome and cancers in the digestive system.
Escherichia coli
and
Bacteroides fragilis
have been found to be enriched in colorectal mucosal tissues from patients with familial adenomatous polyposis that is caused by germline
APC
mutations. In addition, recent studies have found enrichment of certain oral bacteria, viruses, and fungi in tumor tissue and fecal specimens from patients with gastrointestinal cancer. An integrative approach is required to elucidate the role of microorganisms in the pathogenic process of gastrointestinal cancers, which develop through the accumulation of somatic genetic and epigenetic alterations in neoplastic cells, influenced by host genetic variations, immunity, microbiome, and environmental exposures. The transdisciplinary field of molecular pathological epidemiology (MPE) offers research frameworks to link germline genetics and environmental factors (including diet, lifestyle, and pharmacological factors) to pathologic phenotypes. The integration of microbiology into the MPE model (microbiology–MPE) can contribute to better understanding of the interactive role of environment, tumor cells, immune cells, and microbiome in various diseases. We review major clinical and experimental studies on the microbiome, and describe emerging evidence from the microbiology–MPE research in gastrointestinal cancers. Together with basic experimental research, this new research paradigm can help us to develop new prevention and treatment strategies for gastrointestinal cancers through targeting of the microbiome.
Background
Controlling Nutritional Status (CONUT), as calculated from serum albumin, total cholesterol concentration, and total lymphocyte count, was previously shown to be useful for nutritional ...assessment. The current study investigated the potential use of CONUT as a prognostic marker in gastric cancer patients after curative resection.
Methods
Preoperative CONUT was retrospectively calculated in 416 gastric cancer patients who underwent curative resection at Kumamoto University Hospital from 2005 to 2014. The patients were divided into two groups: CONUT-high (≥4) and CONUT-low (≤3), according to time-dependent receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated.
Results
CONUT-high patients were significantly older (
p
< 0.001) and had a lower body mass index (
p
= 0.019), deeper invasion (
p
< 0.001), higher serum carcinoembryonic antigen (
p
= 0.037), and higher serum carbohydrate antigen 19-9 (
p
= 0.007) compared with CONUT-low patients. CONUT-high patients had significantly poorer overall survival (OS) compared with CONUT-low patients according to univariate and multivariate analyses (hazard ratio: 5.09, 95% confidence interval 3.12–8.30,
p
< 0.001). In time-dependent ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 5-year OS than the neutrophil lymphocyte ratio, the Modified Glasgow Prognostic Score, or pStage. When the time-dependent AUC curve was used to predict OS, CONUT tended to maintain its predictive accuracy for long-term survival at a significantly higher level for an extended period after surgery when compared with the other markers tested.
Conclusions
CONUT is useful for not only estimating nutritional status but also for predicting long-term OS in gastric cancer patients after curative resection.
Cellular senescence in cancer development is known to have tumor‐suppressive and tumor‐promoting roles. Recent studies have revealed numerous molecular mechanisms of senescence followed by ...senescence‐associated secretory phenotype induction and showed the significance of senescence on both sides. Cellular senescence in stromal cells is one of the reasons for therapeutic resistance in advanced cancer; thus, it is an inevitable phenomenon to address while seeking an effective cancer treatment strategy. This review summarizes the molecular mechanisms regarding cellular senescence, focusing on the dual roles played by senescence, and offers some direction toward successful treatments targeting harmful senescent cells.
From noncancerous to precancerous stages, immune cells act as senescent surveillance agents by eliminating premalignant senescent cells. On the other hand, in advanced stages of cancer, senescent stromal cells secrete senescence‐associated secretory phenotype factors to promote cancer cell proliferation, metastasis, and angiogenesis through interactions with tumor cells. We focus on the dual nature of senescence depending on the surrounding circumstances and offer some proposals toward successful senolytic strategies targeting harmful senescent cells.
Current non-invasive scores for the assessment of severity of non-alcoholic fatty liver disease (NAFLD) and identification of patients with non-alcoholic steatohepatitis (NASH) have insufficient ...performance to be included in clinical routine. In the current study, we developed a novel machine learning approach to overcome the caveats of existing approaches.
Non-invasive parameters were selected by an ensemble feature selection (EFS) from a retrospectively collected training cohort of 164 obese individuals (age: 43.5±10.3y; BMI: 54.1±10.1kg/m2) to develop a model able to predict the histological assessed NAFLD activity score (NAS). The model was evaluated in an independent validation cohort (122 patients, age: 45.2±11.75y, BMI: 50.8±8.61kg/m2).
EFS identified age, γGT, HbA1c, adiponectin, and M30 as being highly associated with NAFLD. The model reached a Spearman correlation coefficient with the NAS of 0.46 in the training cohort and was able to differentiate between NAFL (NAS≤4) and NASH (NAS>4) with an AUC of 0.73. In the independent validation cohort, an AUC of 0.7 was achieved for this separation. We further analyzed the potential of the new model for disease monitoring in an obese cohort of 38 patients under lifestyle intervention for one year. While all patients lost weight under intervention, increasing scores were observed in 15 patients. Increasing scores were associated with significantly lower absolute weight loss, lower reduction of waist circumference and basal metabolic rate.
A newly developed model (http://CHek.heiderlab.de) can predict presence or absence of NASH with reasonable performance. The new score could be used to detect NASH and monitor disease progression or therapy response to weight loss interventions.
The effectiveness of current chemotherapies for cancer is gradually progressing; however achieving a complete cure through chemotherapy is still difficult and has been the main goal in treatment of ...advanced cancer. Drug resistance is an issue in cancer therapy, therefore increasing numbers of investigations into drug resistance have focused on the characteristics of the cancer cells themselves. The interaction between the tumor microenvironment (TME) and cancer cells is also intimately involved in the development of drug resistance. Cancer‐associated fibroblasts (CAFs) are a predominant component of the TME and affect tumor progression by secreting soluble factors. This review summarizes the most up‐to‐date knowledge of CAFs and drug resistance in cancer, with a focus on factors secreted from CAFs including proteins, cytokines, extracellular vesicles, and metabolites. A perspective on the potential role of anti‐CAF therapies in overcoming CAF‐induced drug resistance is also discussed.
Drug resistance is a main issue for anticancer therapies. Cancer‐associated fibroblasts (CAFS) have a huge effect in promoting drug resistance. This review summarizes the current perspectives on the role of CAFs in chemoresistance.
Emerging evidence indicates that gut microbiome plays a crucial role in the cancer pathogenesis. Although
(
) is associated with poor prognosis in multiple cancers, its clinical significance in ...predicting response to chemotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains unclear.
The
levels were quantified by qPCR assays in tumor tissues from 551 patients with ESCC from two independent cohorts, including 101 patients who received neoadjuvant chemotherapy prior to curative resection. Associations between
burden and recurrence-free survival (RFS), as well with chemotherapeutic response were evaluated using response evaluation criteria in solid tumors (RECISTs), primary tumor metabolic response defined by maximum standardized uptake value (SUV
) changes in positron emission tomography-CT (PET/CT), and pathologic tumor regression grade (TRG).
High burden of
in patients with ESCC associated with poor RFS in both training log-rank
= 0.02; HR = 1.61;
= 0.03 and validation cohorts (log-rank
= 0.003; HR = 1.96;
= 0.004). Importantly, patients with ESCC with high levels of
displayed poor chemotherapeutic response for all three evaluation methods: RECIST (
= 0.04), SUV
change in PET/CT (
= 0.0004), and TRG (
= 0.003).
We conclude that high levels of intratumoral
have a prognostic significance for predicting poor RFS in patients with ESCC. More importantly, our data indicates that higher
burden correlates with poor response to neoadjuvant chemotherapy, suggesting the possibility that an antibiotic intervention against this bacterium may significantly improve therapeutic response in patients with ESCC.
The 2020 impact factor (IF being more than 5) in the surgical area, especially gastroenterology, is as follows: JAMA Surgery (IF = 14.766), Annals of Surgery (12.969), Endoscopy (10.093), American ...Journal of Transplantation (8.086), Digestive Endoscopy (7.559), Hepatobiliary Surgery and Nutrition (7.293), Journal of Hepato-Biliary-Pancreatic Sciences (7.027), British Journal of Surgery (6.939), American Journal of Surgical Pathology (6.394), JAMA Otolaryngology-Head & Neck Surgery (6.223), Journal of the American College of Surgeons (6.113), International Journal of Surgery (6.071), Liver Transplantation (5.799), and Annals of Surgical Oncology (5.344). Let's all agree here and now that we will attain a higher state and lead the world in the field of gastroenterological surgery. ...once we have an IF of more than 5, we hope many high-quality papers will be submitted to AGS from all over the world.
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