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Histopathology of tongue proliferative lesions developed in male TSOD mice treated with 20 ppm 4-NQO in drinking water: (a) moderate dysplasia; (b) squamous cell papilloma; (c) carcinoma in situ; (d) invasive squamous cell carcinoma. Hematoxylin and eosin stain, bar = 100 µm.
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Background
Obesity and diabetes mellitus are associated with lifestyle-related carcinogenesis. They are also risk factors of esophageal adenocarcinoma, but there are only a few reports on association between obesity/diabetes and development of squamous cell carcinoma in the oral cavity and esophagus. In this study, we therefore aimed to determine w...
Context in source publication
Context 1
... treatment induced proliferative lesions in the tongue and esophagus of TSOD and TSNO mice. Proliferative lesions developed in the tongue (Fig. 1) and esophagus ( Fig. 2) in- cluded squamous cell dysplasia, papilloma and carcinomas. The incidences and multiplicities are summarized in Tables 3 and 4. The incidence and multiplicities of tongue proliferative lesions were comparable in the TSOD and TSNO mice (Table 3). On the other hand, the incidences of squamous cell papil- loma ...
Citations
... Although the mechanism still needs to be elucidated, some studies suggest potential mechanisms between metabolic factors and squamous cell carcinomas. In a recent experiment with mice, obese/diabetic mice were more susceptible to ESCC than control mice (30). In addition, several proinflammatory cytokines were higher in obese/diabetic mice than in control mice. ...
Background:
Metabolic syndrome (MetS) is believed to increase the risk of esophageal cancer. However, most studies have been conducted in Western countries, focusing on esophageal adenocarcinoma (EAC). We aimed to investigate the association between MetS and risk of esophageal cancer in nationally representative large dataset in Korea, where esophageal squamous cell carcinoma (ESCC) is predominant.
Methods:
We analyzed the health examinations and claims data from the Korean National Health Insurance Service (NHIS). A total of 6,795,738 subjects who received an NHIS provided health examination in 2009 (index year) were included. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association of MetS and its components (elevated waist circumference, blood pressure, triglycerides, fasting blood glucose, reduced high-density lipoprotein cholesterol) with the risk of esophageal cancer.
Results:
During a mean (± SD) follow-up of 8.2 (± 1.1) years, 6,414 cases of esophageal cancer occurred. MetS was associated with an increased risk of esophageal cancer (aHR 1.11, 95% CI 1.05-1.18). Among the components of MetS, elevated waist circumference (1.24, 1.16-1.33), high blood pressure (1.29, 1.22-1.37), and fasting blood glucose (1.16, 1.11-1.22) were associated with increased risk of esophageal cancer.
Conclusions:
MetS was associated with an increased risk of esophageal cancer.
Impact:
Our findings suggest that individuals with MetS may be at increased risk for esophageal cancer, specifically ESCC. Further studies are needed to establish the relationship between MetS and esophageal cancer.
... 14 IL-17 plays an important role in a variety of human tumors, and a study has shown that IL-17 also plays a key role in esophageal carcinogenesis. 15, 16 4-Nitroquinoline N-oxide (4NQO) is a carcinogen, which can induce esophageal carcinogenesis in C57BL/6J mice, and it is often used as an experimental esophageal cancer model. 17 MANL are also often used as a tea-like drink or medicine in China, but the related product has not been fully developed and utilized due to lack of in-depth research and development. ...
Background
The aim of this study was to observe the preventive effect of flavonoids extracted from Malus asiatica Nakai leaves (FMANL) on esophageal cancer in mice, especially the ability of FMANL to regulate the interleukin 17 (IL-17) signaling pathway during this process.
Materials and Methods
The C57BL/6J mice were treated with 4-nitroquinoline N-oxide (4NQO) to induce esophageal cancer, and the visceral tissue index and the serum and esophageal tissue indexes of mice were used to verify the effect of FMANL.
Results
The experimental results showed that FMANL can effectively control the changes in visceral tissue caused by esophageal cancer. FMANL could increase the cytokine levels of interleukin 10 (IL-10), monocyte chemotactic protein 1 (MCP-1) and decrease the cytokine levels of tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), interleukin 6 (IL-6), and interleukin 12p70 (IL-12p70) in serum of mice with esophageal cancer. FMANL could also reduce CD3⁺, CD4⁺, and CD8⁺ and enhance CD19⁺ mouse peripheral blood lymphocytes. The results of qPCR and Western blot analysis showed that FMANL could down-regulate the mRNA and protein expression levels of IL-17, interleukin 23 (IL-23), interleukin 1 beta (IL-1β), chemokine (C-X-C) ligand 1 (CXCL1), chemokine (C-X-C) ligand 2 (CXCL2), S100 calcium-binding protein A8 (S100A8), S100 calcium-binding protein A9 (S100A9), matrix metalloprotein 9 (MMP-9), and matrix metalloprotein 13 (MMP-1) in mice with esophageal cancer. High-performance liquid chromatography (HPLC) detection showed that FMANL contained 10 chemicals, including rutin, hyperoside, isoquercitrin, dihydroquercetin, quercitrin, hesperidin, myricetin, baicalin, neohesperidin dihydrochalcone, and quercetin.
Conclusion
It could be concluded that FMANL can effectively prevent experimentally induced esophageal cancer in mice, and its effects might be obtained from 10 compounds present in FMANL.
... There are many common risk factors for DM and HNSCC, including advanced age, poor diet and lifestyle, and environmental factors [32]. In Asia, Tseng found a higher risk of HN cancer in individuals with DM than in those without [33], and a retrospective study of patients with oral SCC (n=600) and controls (n=574) found that there was a higher prevalence of DM in the former (24.3% versus 11.1%) [34]. ...
... Hyperlipidemia is a risk factor for oral cancer [33]. In addition, obese and diabetic Tsumura Suzuki Obese Diabetic mice are susceptible to 4-nitroquinoline 1-oxide-induced esophageal carcinogenesis, suggesting that obesity and DM are risk factors for esophageal SCC [32]. Dysregulation of 72 lipid metabolites has been demonstrated in oral SCC, and a combination of TGFB1 (transforming growth factor-β1), SPP1 (secreted phosphoprotein-1), and SERPINNE1 (Serine protease-1) is useful for predicting oral SCC prognosis [59]. ...
In recent years, the incidence of diabetes mellitus and cancer has increased sharply; indeed, these have become the two most important diseases threatening health and survival. Head and neck (HN) tumors are the sixth most common malignancies in humans. Numerous studies have shown that there are many common risk factors for diabetes mellitus and HN squamous cell carcinoma, including advanced age, poor diet and lifestyle, and environmental factors. However, the mechanism linking the two diseases has not been identified. A number of studies have shown that diabetes affects the development, metastasis, and prognosis of HN cancer, potentially through the associated hyperglycemia, hyperinsulinemia and insulin resistance, or chronic inflammation. More recent studies show that metformin, the first-line drug for the treatment of type 2 diabetes, can significantly reduce the risk of HN tumor development and reduce mortality in diabetic patients. Here, we review recent progress in the study of the relationship between diabetes mellitus and HN carcinogenesis, and its potential mechanisms, in order to provide a scientific basis for the early diagnosis and effective treatment of these diseases.
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Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly diseases. In our previous comprehensive genomics study, we found that family with sequence similarity 135 member B ( FAM135B ) was a novel cancer-related gene, yet its biological functions and molecular mechanisms remain unclear. In this study, we demonstrate that the protein levels of FAM135B are significantly higher in ESCC tissues than in precancerous tissues, and high expression of FAM135B correlates with poorer clinical prognosis. Ectopic expression of FAM135B promoted ESCC cell proliferation in vitro and in vivo , likely through its direct interaction with growth factor GRN, thus forming a feedforward loop with AKT/mTOR signaling. Patients with ESCC with overexpression of both FAM135B and GRN had worse prognosis; multivariate Cox model analysis indicated that high expression of both FAM135B and GRN was an independent prognostic factor for patients with ESCC. FAM135B transgenic mice bore heavier tumor burden than wild-type mice and survived a relatively shorter lifespan after 4-nitroquinoline 1-oxide treatment. In addition, serum level of GRN in transgenic mice was higher than in wild-type mice, suggesting that serum GRN levels might provide diagnostic discrimination for patients with ESCC. These findings suggest that the interaction between FAM135B and GRN plays critical roles in the regulation of ESCC progression and both FAM135B and GRN might be potential therapeutic targets and prognostic factors in ESCC.
Significance:
These findings investigate the mechanisms of FAM135B in promoting ESCC progression and suggest new potential prognostic biomarkers and therapeutic targets in patients with ESCC.</p
Objective
To compare the effects of dietary fat and sex on murine oral squamous cell carcinoma pathology.
Materials and methods
Male and female C57Bl/6 mice (36/sex) received a low‐fat (10 kcal%) or high‐fat (60 kcal%) diet. Water (control), vehicle, or 4‐nitroquinoline‐1‐oxide in vehicle (50 µg/ml) was provided for 17 weeks followed by 6 additional weeks of water. Oral lesion development was recorded weekly. Histopathologic changes in tongues were examined and T cells (CD3+), macrophages (CD68+), and neutrophils (Ly6+) were quantified.
Results
All 4‐nitroquinoline‐1‐oxide treated mice developed oral tumors. High‐fat diet exacerbated pathology, demonstrated by an increased final tumor burden (10.9 ± 4.5 vs 7.9 ± 2.5, mm/mouse, p < 0.05; high‐fat diet vs. low‐fat diet, respectively), and a greater histopathology score. When dietary groups were combined, 4‐nitroquinoline‐1‐oxide treated males displayed higher histopathology scores than females (4.2 ± 0.3 vs. 3.6 ± 0.2, respectively, p< 0.05). Lymphoid cell infiltration was greater in the 4‐nitroquinoline‐1‐oxide mouse tongues than controls: T cells (14.0 vs 0.96 cells/mm²), macrophages (3.6 vs 1.8 cells/mm²), and neutrophils (12.0 vs 0.38 cells/mm²).
Conclusion
High‐fat diet and male sex increased the pathology of 4‐nitroquinoline‐1‐oxide ‐induced oral cancer. Elevated lymphoid cell infiltration contributed to disease pathology.
