The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPK/mTOR pathway in vitro and in vivo

Galectin-9 (Gal-9) enhances tumor immunity mediated by T cells, macrophages, and dendritic cells. Its expression level in various cancers correlates with prognosis. Furthermore, Gal-9 directly induces apoptosis in various cancers; however, its mechanism of action and bioactivity has not been clarified. We evaluated Gal-9 antitumor effect against esophageal squamous cell carcinoma (ESCC) to analyze the dynamics of apoptosis-related molecules, elucidate its mechanism of action, and identify relevant changes in miRNA expressions. KYSE-150 and KYSE-180 cells were treated with Gal-9 and their proliferation was evaluated. Gal-9 inhibited cell proliferation in a concentration-dependent manner. The xenograft mouse model established with KYSE-150 cells was administered with Gal-9 and significant suppression in the tumor growth observed. Gal-9 treatment of KYSE-150 cells increased the number of Annexin V-positive cells, activation of caspase-3, and collapse of mitochondrial potential, indicating apoptosis induction. c-Jun NH₂-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) phosphorylation were activated and could be involved in apoptosis. Therefore, Gal-9 induces mitochondria-mediated apoptosis of ESCC and inhibits cell proliferation in vitro and in vivo with JNK and p38 activation.

Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy. Telmisartan, an angiotensin II type 1 (AT1) receptor blocker (ARB) and a widely used antihypertensive, has been shown to inhibit proliferation of various cancer types. This study evaluated the effects of telmisartan on human ESCC cell proliferation in vitro and in vivo and sought to identify the microRNAs (miRNAs) involved in these antitumor effects. We examined the effects of telmisartan on three human ESCC cell lines (KYSE150, KYSE180, and KYSE850). Telmisartan inhibited proliferation of these three cell lines by inducing S-phase arrest, which was accompanied by decreased expression of cyclin A2, cyclin-dependent kinase 2, and other cell cycle-related proteins. Additionally, telmisartan reduced levels of phosphorylated ErbB3 and thrombospondin-1 in KYSE180 cells. Furthermore, expression of miRNAs was remarkably altered by telmisartan in vitro. Telmisartan also inhibited tumor growth in vivo in a xenograft mouse model. In conclusion, telmisartan inhibited cell proliferation and tumor growth in ESCC cells by inducing cell-cycle arrest.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. Sorafenib has been used as a first-line systemic treatment for over a decade. However, resistance to sorafenib limits patient response and presents a major hurdle during HCC treatment. Lenvatinib has been approved as a first-line systemic treatment for advanced HCC and is the first agent to achieve non-inferiority against sorafenib. Therefore, in the present study, we evaluated the inhibition efficacy of lenvatinib in sorafenib-resistant HCC cells. Only a few studies have been conducted on this topic. Two human HCC cell lines, Huh-7 and Hep-3B, were used to establish sorafenib resistance, and in vitro and in vivo studies were employed. Lenvatinib suppressed sorafenib-resistant HCC cell proliferation mainly by inducing G1 cell cycle arrest through ERK signaling. Hep-3B sorafenib-resistant cells showed partial cross-resistance to lenvatinib, possibly due to the contribution of poor autophagic responsiveness. Overall, the findings suggest that the underlying mechanism of lenvatinib in overcoming sorafenib resistance in HCC involves FGFR4-ERK signaling. Lenvatinib may be a suitable second-line therapy for unresectable HCC patients who have developed sorafenib resistance and express FGFR4.

Metabolic syndrome is a cluster of metabolic abnormalities and is defined as the presence of three or more of the following factors: increased waist circumference, elevated triglycerides, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose. Obesity, which is accompanied by metabolic dysregulation often manifested in the metabolic syndrome, is an established risk factor for many cancers. Adipose tissue, particularly visceral fat, is an important metabolic tissue as it secretes systemic factors that alter the immunologic, metabolic, and endocrine milieu and also promotes insulin resistance. Within the growth-promoting, proinflammatory environment of the obese state, cross-talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, adipocytokines, and other mediators that may enhance cancer risk and progression. This paper synthesizes the evidence on key molecular mechanisms underlying the obesity-cancer link.

Endoscopic full-thickness resection (EFTR) is a procedure that makes it possible to access the lesions that are on the wall of the digestive tract via the shortest distance through the mouth. Because of the ultra-minimal invasive nature of the treatment, pure EFTR is a highly promising surgical procedure that allows the radical excision of full-thickness layers of digestive tract tumors using only a flexible endoscope. There are 2 types of EFTR methods: exposed and non-exposed. Considering the risks of contracting infection and intraperitoneal dissemination of tumor cells, non-exposed EFTR is an ideal method. However, a number of issues remain unresolved, including the method for performing a full-thickness suture under endoscopic view and the challenge of securing the operating field in the case of gastrointestinal tract collapse. Moreover, advances in the development of equipment such as full-thickness suturing devices would be helpful to make this therapeutic procedure the most minimally invasive endoscopic surgery ever.