NOX1/NADPH Oxidase Expressed in Colonic Macrophages Contributes to the Pathogenesis of Colonic Inflammation in Trinitrobenzene Sulfonic Acid-Induced Murine Colitis.

NOX1/NADPH oxidase, a nonphagocytic isoform of reactive oxygen species-producing enzymes, is highly expressed in the colon, but the physiologic and pathophysiologic roles of this isoform are not fully understood. The present study investigated the role of NOX1 in the development of colonic inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model. Intrarectal injection of TNBS caused severe colitis accompanied by body weight loss, diarrhea, and increased myeloperoxidase (MPO) activity in wild-type (WT) mice. In contrast, the severity of colitis was significantly attenuated in NOX1-deficient (NOX1KO) mice (the inhibitions of macroscopic damage score, body weight loss, diarrhea score, and MPO activity were 73.1%, 36.8%, 83.3%, and 98.4%, respectively). TNBS-induced upregulation of inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1ß), chemokines (CXCL1 and CXLC2), and inducible nitric oxide synthase (iNOS) was also significantly less in NOX1KO than in WT mice (the inhibitions were 100.8%, 89.0%, 63.5%, 96.7%, and 97.1%, respectively). Expression of NOX1 mRNA was detected not only in the lamina propria but also in peritoneal macrophages isolated from WT mice. Increased expression of TNF-α, IL-1ß, and iNOS in peritoneal macrophages exposed to lipopolysaccharide was significantly attenuated in macrophages isolated from NOX1KO mice (68.1%, 67.0%, and 79.3% inhibition, respectively). These findings suggest that NOX1/NADPH oxidase plays an important role in the pathogenesis of TNBS-induced colonic inflammation via upregulation of inflammatory cytokines, chemokines, and iNOS. NOX1 in colonic macrophages may become a potential target in pharmacologic intervention for inflammatory bowel disease.

Clinicopathological Features of Buccal Squamous Cell Carcinoma with Focus on Patients Who Never Smoke and Never Drink.

Introduction Oral carcinoma has been reported at a substantial proportion in patients who never smoke and never drink. However, the proportion may vary by subsite and ethnicity. Objective We aimed to determine the clinicopathological features of buccal squamous cell carcinoma (SCC) in a Japanese population. Methods We retrospectively analyzed the records of patients diagnosed with buccal SCC at our institution from September 2002 to November 2015. We reviewed the gender, age, tumor status, treatment, smoking, alcohol drinking, multiple primary cancers, and prognosis of the patients. The overall and cause-specific survival rates were calculated, and the effects of clinicopathological variables were assessed by univariate analysis. Furthermore, the cause of death was evaluated. Results Among the 63 patients (men: 38; women: 25) included in the present study, 29 (46.0%) never smoked or drank. Women were almost 5 years older than men ( p = 0.014). The number of women in the group who never smoked or drank was disproportionately higher than that of those in the smoker or drinker groups ( p < 0.001). In total, 29 patients (46.0%) had 59 multiple primary cancers, including 26 oral cancers. Surgeries and radiotherapy were performed in 57 (90.5%) and 6 (9.5%) cases, respectively. The 5-year overall survival and disease-specific survival rates were 74.6 and 78.8%, respectively. Conclusion Our study confirms that buccal SCC may develop in older adult Japanese patients, especially in women who have never smoked or drank. These patients could be at risk for second primary malignancy.

Clinicopathological Features of Buccal Squamous Cell Carcinoma with Focus on Patients Who Never Smoke and Never Drink

Abstract Introduction Oral carcinoma has been reported at a substantial proportion in patients who never smoke and never drink. However, the proportion may vary by subsite and ethnicity. Objective We aimed to determine the clinicopathological features of buccal squamous cell carcinoma (SCC) in a Japanese population. Methods We retrospectively analyzed the records of patients diagnosed with buccal SCC at our institution from September 2002 to November 2015. We reviewed the gender, age, tumor status, treatment, smoking, alcohol drinking, multiple primary cancers, and prognosis of the patients. The overall and cause-specific survival rates were calculated, and the effects of clinicopathological variables were assessed by univariate analysis. Furthermore, the cause of death was evaluated. Results Among the 63 patients (men: 38; women: 25) included in the present study, 29 (46.0%) never smoked or drank. Women were almost 5 years older than men (p = 0.014). The number of women in the group who never smoked or drank was disproportionately higher than that of those in the smoker or drinker groups (p < 0.001). In total, 29 patients (46.0%) had 59 multiple primary cancers, including 26 oral cancers. Surgeries and radiotherapy were performed in 57 (90.5%) and 6 (9.5%) cases, respectively. The 5-year overall survival and disease-specific survival rates were 74.6 and 78.8%, respectively. Conclusion Our study confirms that buccal SCC may develop in older adult Japanese patients, especially in women who have never smoked or drank. These patients could be at risk for second primary malignancy.