Obesity, type 2 diabetes mellitus (T2DM) and aging are associated with pancreatic cancer risk, but the mechanisms of pancreatic cancer development caused by these factors are not clearly understood. Syrian golden hamsters are susceptible to N‐nitrosobis(2‐oxopropyl)amine (BOP)‐induced pancreatic carcinogenesis. Aging, BOP treatment and/or a high‐fat diet cause severe and scattered fatty infiltration (FI) of the pancreas with abnormal adipokine production and promote pancreatic ductal adenocarcinoma (PDAC) development. The KK‐A^y mouse, a T2DM model, also develops severe and scattered FI of the pancreas. Treatment with BOP induced significantly higher cell proliferation in the pancreatic ducts of KK‐A^y mice, but not in those of ICR and C57BL/6J mice, both of which are characterized by an absence of scattered FI. Thus, we hypothesized that severely scattered FI may be involved in the susceptibility to PDAC development. Indeed, severe pancreatic FI, or fatty pancreas, is observed in humans and is associated with age, body mass index (BMI) and DM, which are risk factors for pancreatic cancer. We analyzed the degree of FI in the non‐cancerous parts of PDAC and non‐PDAC patients who had undergone pancreatoduodenectomy by histopathology and demonstrated that the degree of pancreatic FI in PDAC cases is significantly higher than that in non‐PDAC controls. Moreover, the association with PDAC is positive, even after adjusting for BMI and the prevalence of DM. Accumulating evidence suggests that pancreatic FI is involved in PDAC development in animals and humans, and further investigations to clarify the genetic and environmental factors that cause pancreatic FI are warranted.

The criteria for metabolic syndrome include obesity, hyperlipidemia, type 2 diabetes, and hypertension. Several cancers, including colon cancer, are demonstrated to be associated with metabolic syndrome.¹ x 1 Trevisan, M., Liu, J., Muti, P. et al. Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev. 2001; 10: 937–941 PubMed | Google Scholar See all References ^{, 2} x 2 Colangelo, L.A., Gapstur, S.M., Gann, P.H. et al. Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev. 2002; 11: 385–391 PubMed | Google Scholar See all References ^{, 3} x 3 Ahmed, R.L., Schmitz, K.H., Anderson, K.E. et al. The metabolic syndrome and risk of incident colorectal cancer. Cancer. 2006; 107: 28–36 Crossref | PubMed | Scopus (219) | Google Scholar See all References ^{, 4} x 4 Stocks, T., Lukanova, A., Johansson, M. et al. Components of the metabolic syndrome and colorectal cancer risk; a prospective study. Int J Obes (Lond). 2008; 32: 304–314 Crossref | PubMed | Scopus (92) | Google Scholar See all References ^{, 5} x 5 Giovannucci, E. Insulin and colon cancer. Cancer Causes Control. 1995; 6: 164–179 Crossref | PubMed | Scopus (610) | Google Scholar See all References Obesity-associated cancers are common in Western countries, and they are currently increasing in Eastern countries as well. However, the mechanisms underlying how metabolic syndrome is associated with carcinogenesis remain to be fully understood. Insulin resistance, with hyperinsulinemia, hyperlipidemia, and hyperglycemia, are suggested to be involved in the promotion of colon cancer growth. In addition, dysregulation of adipocytokines, such as adiponectin (APN), leptin, plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor−α (TNFα) has been shown to play a crucial role in the pathogenesis of the metabolic syndrome and postulated to promote carcinogenesis.⁶ x 6 Matsuzawa, Y. The metabolic syndrome and adipocytokines. FEBS Lett. 2006; 580: 2917–2921 Abstract | Full Text | Full Text PDF | PubMed | Scopus (373) | Google Scholar See all References In human clinical studies, it has been reported that the amount of visceral fat positively correlates with colon adenoma risk, and serum APN levels show a negative correlation.⁷ x 7 Otake, S., Takeda, H., Suzuki, Y. et al. Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance. Clin Cancer Res. 2005; 11: 3642–3646 Crossref | PubMed | Scopus (178) | Google Scholar See all References

Background: Randomized controlled studies have investigated the short-term effect of soy product intake on blood pressure (BP) in normotensive people

Edible plant-derived nanovesicles have been explored as effective materials for preventing colorectal cancer (CRC) incidence, dependent on gene status, as a K-Ras-activating mutation via the macropinocytosis pathway. Approximately 70% of CRC harbors the p53 mutation, which is strongly associated with a poor prognosis for CRC. However, it has not been revealed whether p53 inactivation activates the macropinocytosis pathway or not. In this study, we investigated parental cells, wild-type or null for p53 treated with Citrus limon L.-derived nanovesicles, as potential materials for CRC prevention. Using ultracentrifugation, we obtained C. limon L.-derived nanovesicles, the diameters of which were approximately 100 nm, similar to that of the exosomes derived from mammalian cells. C. limon L.-derived nanovesicles showed inhibitory effects on cell growth in not p53-wild, but also in p53-inactivated CRC cells. Furthermore, we revealed that the macropinocytosis pathway is activated by p53 inactivation and C. limon L.-derived nanovesicles were up taken via the macropinocytosis pathway. Notably, although C. limon L.-derived nanovesicles contained citrate, the inhibitory effects of citrate were not dependent on the p53 status. We thus provide a novel mechanism for the growth inhibition of C. limon L.-derived nanovesicles via macropinocytosis and expect to develop a functional food product containing them for preventing p53-inactivation CRC incidence.