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Simple Summary: Cancer-associated fibroblasts (CAFs) are a major component of the stroma in oral squamous cell carcinoma (OSCC) and are considered important therapeutic targets. In this study, we demonstrated that aortic carboxypeptidase-like protein (ACLP) is highly expressed in CAFs of OSCC, thereby activating them. Cancer cells induce ACLP expression in CAFs through the TGF-β1 signaling pathway, and CAF-derived ACLP enhances the migration and infiltration of cancer cells. Furthermore, ACLP co-expresses with collagen and shows an inverse correlation with tumor infiltration of CD8+ T lymphocytes. Our data suggest that targeting ACLP could be a potential approach for stromal-targeted therapy and a novel target for cancer immunotherapy. We previously showed that upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in vascular endothelial cells promotes tumor angiogenesis. In the present study, we aimed to clarify the role of stromal AEBP1/ACLP expression in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis showed that ACLP is abundantly expressed in cancer-associated fibroblasts (CAFs) in primary OSCC tissues and that upregulated expression of ACLP is associated with disease progression. Analysis using CAFs obtained from surgically resected OSCCs showed that the expression of AEBP1/ACLP in CAFs is upregulated by co-culture with OSCC cells or treatment with TGF-β1, suggesting cancer-cell-derived TGF-β1 induces AEBP1/ACLP in CAFs. Collagen gel contraction assays showed that ACLP contributes to the activation of CAFs. In addition, CAF-derived ACLP promotes migration, invasion, and in vivo tumor formation by OSCC cells. Notably, tumor stromal ACLP expression correlated positively with collagen expression and correlated inversely with CD8+ T cell infiltration into primary OSCC tumors. Boyden chamber assays suggested that ACLP in CAFs may attenuate CD8+ T cell migration. Our results suggest that stromal ACLP contributes to the development of OSCCs, and that ACLP is a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background and Aim: Insulin‐like growth factor‐1 (IGF1) is a potent mitogen and is inhibited by IGF‐binding protein‐3 (IGFBP3). High serum IGF1 and low IGFBP3 are associated with increased risk of several carcinomas. Here, we assessed the relationship of these peptides with the risk of gastrointestinal malignancies, in a prospective case–control study nested in the Japan Collaborative Cohort Study. Methods: The analysis involved 916 cases who had been diagnosed as gastrointestinal malignancies (C15–25) and 2306 controls. To estimate odds ratios for incidence of malignancies associated with these levels, a conditional logistic model was used. Results: Both higher total and free IGFBP3 were associated with a decreased risk of tumor (P for trend < 0.001 and = 0.003, respectively). People in the second to fifth quintiles had lower risk compared to the first quintile (odds ratios ranged 0.532–0.650 and 0.582–0.725, respectively). After adjustment for IGF1, body mass index, drinking, and smoking, total IGFBP3 was inversely correlated with cancer risk (P for trend = 0.031). After adjustment, free IGFBP3 was inversely associated with the risk (P for trend = 0.007). Although total IGF1 was inversely correlated with tumor risk, it was not after controlling for IGFBP3 (P for trend = 0.007 and 0.589, respectively). Free IGF1 was not associated with the risk (P for trend = 0.361). Limiting subjects to those followed for over 3 years reinforced the inverted relationships of total and free IGFBP3 with risk for tumors (P for trend = 0.005 and 0.008, respectively). Conclusion: Both total and free IGFBP3 may be inversely associated with the incidence of gastrointestinal malignancies. [ABSTRACT FROM AUTHOR]

Aim: Interval gastric cancers (IGC) are defined as those diagnosed after negative results of endoscopy carried out within the past 10 years. We aimed to investigate the characteristics of IGC and the natural history of gastric cancer (GC) from a retrospective view of endoscopic images of older patients with IGC. Methods: We retrospectively reviewed endoscopic images of 240 patients with GC who were aged >60 years. We compared past endoscopic images with newer ones, in which GC was diagnosed. IGC were classified into two categories: missed cancers and new cancers. Results: Of the 240 patients with GC, 32 had past endoscopic images that qualified for a precise review. A total of 14 cases involved new cancers, whereas 18 involved missed cancers. Most of the IGC were stage I for at least 2 years; however, a small subset was unresectable at >2 years after a negative endoscopy. Furthermore, the rate of endoscopic treatment was significantly higher for IGC compared with that for non‐IGC. Conclusions: In people aged >60 years, most IGC remain in an early stage for at least 2 years; however, at >2 years after a negative endoscopy, some are unresectable. These results suggest that most early‐stage GC will not develop into advanced cancers within 2 years; thus, a 2‐year interval might be within the permissible range for patients with negative endoscopy results for any lesions. Geriatr Gerontol Int 2018; 18: 997–1002 [ABSTRACT FROM AUTHOR]