Inflammation, especially chronic inflammation, plays a pivotal role in tumorigenesis and metastasis through various mechanisms and is now recognized as a hallmark of cancer and an attractive therapeutic target in cancer. In this review, we discuss recent advances in molecular mechanisms of how inflammation promotes tumorigenesis and metastasis and suppresses anti-tumor immunity in various types of solid tumors, including esophageal, gastric, colorectal, liver, and pancreatic cancer as well as hematopoietic malignancies.

The Ras/Raf/ERK pathway is one of the most frequently dysregulated signaling pathways in various cancers. In some such cancers, Ras and Raf are hotspots for mutations, which cause continuous activation of this pathway. However, in some other cancers, it is known that negative regulators of the Ras/Raf/ERK pathway are responsible for uncontrolled activation. The Sprouty/Spred family is broadly recognized as important negative regulators of the Ras/Raf/ERK pathway, and its expression is downregulated in many malignancies, leading to hyperactivation of the Ras/Raf/ERK pathway. After the discovery of this family, intensive research investigated the mechanism by which it suppresses the Ras/Raf/ERK pathway and its roles in developmental and pathophysiological processes. In this review, we discuss the complicated roles of the Sprouty/Spred family in tumor initiation, promotion, and progression and its future therapeutic potential.

Mixed adenoneuroendocrine carcinoma (MANEC) is defined as a neoplasm composed of both exocrine and endocrine carcinomas, each comprising at least 30% of the tumor. MANEC can occur in various organs of the gastrointestinal tract, including the esophagus, stomach, and colon. We herein provide the first case report of surgically resected MANEC arising in Barrett’s esophagus (BE). A 70-year-old man presenting with abdominal pain was referred to our hospital. Upper endoscopy showed a type 0-IIa + IIc elevated lesion adjacent to BE. According to a biopsy specimen, the elevated lesion was diagnosed as adenocarcinoma with neuroendocrine differentiation. No lymphatic or distant metastasis was detected in the preoperative examination. Laparoscopic distal esophagectomy and proximal gastrectomy were performed, and a diagnosis of MANEC in BE was determined according to the surgically resected specimen. A very rare case of MANEC in BE was detected. BE can be the origin of esophageal MANEC as well as adenocarcinoma. Due to the small number of esophageal or esophagogastric MANEC cases reported, further accumulation of such cases is necessary to recommend an optimal management strategy for esophageal or esophagogastric MANEC.

This study aimed to investigate the efficacy of measuring lymph node size on preoperative CT imaging to predict pathological lymph node metastasis in patients with colon cancer to enhance diagnostic accuracy and improve treatment planning by establishing more reliable assessment methods for lymph node metastasis. We retrospectively analyzed 1,056 patients who underwent colorectal resection at our institution between January 2004 and March 2020. From this cohort, 694 patients with resectable colon cancer were included in the study. We analyzed the relationship between lymph node size on preoperative CT imaging and lymph node metastasis identified on postoperative pathological examination. The optimal cutoff values for the maximum long diameter and short diameter of regional lymph nodes on preoperative CT were identified as 6.5 mm and 5.5 mm, respectively, with an AUC of 0.7794 and 0.7755, respectively. Notably, the predictive accuracy varied by tumor location. Higher cutoff values were observed in the right-sided colon (maximum long diameter: 7.7 mm, maximum short diameter: 5.9 mm) compared to the left-sided colon (maximum long diameter: 5.8 mm, maximum short diameter: 5.2 mm). Lymph node size on preoperative CT is a significant predictor of pathological lymph node metastasis in colon cancer. Notably, the optimal cutoff values for predicting lymph node metastasis vary depending on the specific region within the colon.

The IL6 family of cytokines, including IL6 and leukemia-inhibitory factor (LIF), are induced during inflammation and are also expressed in many types of cancer where they play an important role in tumor development. IL6 family cytokines mainly activate the JAK–STAT3 pathway via the coreceptor, gp130, and IL6 is known to activate the Src family kinase (SFK)–Yes-associated protein (YAP) pathway. The current study investigated the role of autocrine LIF in human esophageal squamous cell carcinoma (ESCC) that highly expresses LIF. LIF knockdown had various effects on cancer cells, including profound changes in gene expression, suppression of cell proliferation, migration/invasion and sphere formation, and induction of apoptosis. Similar to IL6, LIF activated the SFK–YAP pathway as well as the JAK–STAT3 pathway. LIF-induced YAP activation was more important for cancer cell proliferation than LIF-induced STAT3 activation, and concomitant YAP and STAT3 activation completely compensated for the role of LIF in human ESCC growth. We also confirmed that SFK activation and LIF expression were correlated with YAP activation in human ESCC clinical samples. Furthermore, simultaneous inhibition of the SFK–YAP and JAK–STAT3 pathways in human ESCC cells was more effective at suppressing cell proliferation than single inhibition, and autocrine LIF signaling promoted human ESCC growth in vivo. Therefore, the LIF–SFK–YAP axis may represent a new therapeutic target for human ESCC. Implications: Autocrine LIF signaling promotes human ESCC progression via SFK-dependent YAP activation and is a new potential target of treatment for human ESCC.