Polyamines (spermine and spermidine) play many important roles in cellular function and are supplied from the intestinal lumen. We have shown that continuous high polyamine intake inhibits age-associated pathologies in mice. The mechanism by which polyamines elicit these effects was examined. Twenty-four week old Jc1:ICR male mice were fed one of three experimental chows containing different polyamine concentrations. Lifetime intake of high polyamine chow, which had a polyamine content approximately three times higher than regular chow, elevated polyamine concentrations in whole blood, suppressed age-associated increases in pro-inflammatory status, decreased age-associated pathological changes, inhibited age-associated global alteration in DNA methylation status and reduced the mortality in aged mice. Exogenous spermine augmented DNA methyltransferase activity in Jurkat and HT-29 cells and inhibited polyamine deficiency-induced global alteration in DNA methylation status in vitro. In addition, increased polyamine intake was associated with a decreased incidence of colon tumors in BALB/c mice after 1,2-demethylhydrazine administration; 12 mice (60%) in the low polyamine group developed tumors, compared with only 5 mice (25%) in the high polyamine group (Fisher's exact probability = 0.027, p = 0.025). However, increased polyamine intake accelerated the growth of established tumors; maximal tumor diameter in the Low and High groups was 3.85±0.90 mm and 5.50±1.93 mm, respectively (Mann-Whitney test, p = 0.039). Spermine seems to play important roles in inhibiting age-associated and polyamine-deficient induced abnormal gene methylation as well as pathological changes including tumorigenesis.

The purpose of this study was to examine the contribution of dietary polyamines toward preventing cardiovascular disease (CVD). Age-standardized mortality rates as well as other relevant information regarding individuals with CVD were gathered from the World Health Organization and the International Monetary Fund in 48 different European and other Western countries. Food supply data were collected from the database of the United Nations, and the amount of dietary polyamines was estimated by using polyamine concentrations in foods from published sources. The association between CVD mortality and the amount of polyamines was investigated by performing a series of multiple linear regression analyses. Analyses using factors known to modulate the risk of CVD including: Gross Domestic Product (GDP) (standardized regression coefficient (r) = -0.786, p < 0.001) and the amount of fruits, vegetable, nuts, and beans (r = -0.183, p = 0.001) but not including polyamines, showed negative associations with CVD, while smoking rate (r = 0.139, p = 0.041) and whole milk amount (r = 0.131, p = 0.028) showed positive associations with CVD. When the amount of polyamines was added to the analyses as a covariate, GDP (r = -0.864, p < 0.001) and polyamines (r = -0.355, p = 0.007) showed negative associations with CVD, while smoking rate (r = 0.183, p = 0.006) and whole milk (r = 0.113, p = 0.041) showed positive associations with CVD. The inverse association between dietary polyamines and CVD mortality revealed by the present study merits further evaluation.

Abstract.The relationship between host factors and cancer cachexia was investigated. A single cell clone (clone 5 tumor) established from colon 26 adenocarcinoma by limiting dilution cell cloning methods was employed to eliminate the inoculation site-dependent differences in the composition of cell clones. Clone 5 tumor did not provoke manifestations of cancer cachexia when inoculated in subcutaneous tissue. However, when inoculated in the gastrocnemius muscle, the peritoneal cavity or the thoracic cavity of CD2F1 male mice, typical manifestations of cancer cachexia were observed in all groups of mice with intergroup variations. The blood levels of various cytokines, chemokines and hormones were increased but with wide intergroup variations. Analyses by stepwise multiple regression models revealed that serum interleukin-10 was the most significant factor associated with manifestations of cancer cachexia, suggesting the possible involvement of mechanisms similar to cancer patients suffering cancer cachexia. White blood cells, especially neutrophils, seemed to have some roles on the induction of cancer cachexia, because massive infiltrations and an increase in peripheral blood were observed in cachectic mice bearing clone 5 tumors. The amount of malonyl-CoA in liver correlated with manifestations of cancer cachexia, however the mRNA levels of spermidine/spermine N-1 acetyl transferase (SSAT) (of which overexpression has been shown to provoke manifestations similar to cancer cachexia) were not necessarily associated with cancer cachexia. These data suggest that the induction of cancer cachexia depends on the environment in which the tumor grows and that the infiltration of host immune cells into the tumor and the resultant increase in inflammation result in the production of cachectic factors, such as cytokines, leading to SSAT activation. Further, multiple factors likely mediate the mechanisms of cancer cachexia. Finally, this animal model was suitable for the investigation of the mechanisms involved in cachexia of cancer patients.

We report a 75-year-old woman who suffered multiple metachronous osteosclerotic bone metastases 4 years after a distal gastrectomy for early gastric cancer (EGC). The primary tumor was a poorly differentiated adenocarcinoma, which had invaded the submucosal layer, and only one lymph node metastasis was noted. To the best of our knowledge, cases of EGC combined with metachronous osteosclerotic multiple bone and bone marrow metastases that respond to chemoradiotherapy are very rare. In this case, the multiple bone metastases were diagnosed 4 years after surgery. The patient's metastatic tumor was successfully treated using S-1, paclitaxel, and camptothecin, with subsequent irradiation. The patient survived for 24 months after the treatment, without having any major symptoms.

Mucin-producing carcinoma of the gallbladder is very rare. We report here a case of mucin-producing carcinoma of the gallbladder associated with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). A 74-year-old female had been treated with salazosulfapyridine and ursodesoxycholic acid becase of UC and PSC. After 7 years of treatment, laboratory data showed that the liver function took a turn for the worse, and the patient was admitted to our hospital for further examination. Enhanced computed tomography and ultrasonography showed an enlarged gallbladder associated with wall thickening and diffuse papillary protrusion. Endoscopic retrograde cholangiography showed stenosis and dilatation of the bile duct, which were compatible with PSC. Under the diagnosis of an early carcinoma of the gallbladder, we performed simple cholecystectomy. The tumor showed a papillary growth pattern located diffusely in the gallbladder with a massive amount of mucin filling the gallbladder. Histologically, it was diagnosed as a papillary adenocarcinoma localized in the mucosal layer. To the best of our knowledge, this is the first case of mucin-producing carcinoma of the gallbladder associated with PSC and UC. PSC and UC patients should be regarded as a high-risk group not only for cholangiocarcinoma but also carcinoma of the gallbladder.