Naoki Yoshimi

Serous cystadenocarcinoma of the pancreas, a rare disease, developed in a 63-year-old Japanese woman. Pathologic examinations of the pancreatic tumor at the subtotal pancreatectomy showed it to be serous cystadenoma with focal atypical lesions. Three years after the operation, however, metastatic liver nodules were found, and the histologic characteristics of these lesions were quite similar to those of the pancreatic neoplasm. Both primary and metastatic tumors were composed of multiple cysts separated by fibrous septa. The epithelium of cysts was cuboidal and had clear cytoplasm, which had positive results for periodic acid-Schiff (PAS) and negative results for PAS with diastase, Alcian blue, and mucicarmine. To the knowledge of the authors, serous cystic neoplasms of the pancreas have been uniformly benign in biologic behavior. Recently, however, serous cystadenocarcinoma of the pancreas has been reported as a new entity. The current case is the second reported case and might support the existence of serous cystadenocarcinoma of the pancreas.

Modifying effects of a fungal product, flavoglaucin, and four plant-derived chemicals, shikonin, gingerol, oleanolic acid and paeoniflorin, on intestinal carcinogenesis were examined in a rat model using azoxymethane (AOM). A total of 280 male F344 rats, 6 weeks old, were divided into 12 groups. Group 1 (30 rats) was given two subcutaneous injections of 15 mg/kg of AOM at the start of the experiment. Groups 2 (30 rats), 3 (20 rats), 4 (20 rats), 5 (30 rats) and 6 (30 rats) received a test chemical (flavoglaucin, shikonin, gingerol, oleanolic acid or paeoniflorin, respectively) in the diet at a concentration of 0.02% for 3 weeks, during which time AOM was applied, and then kept on basal diet until the end of experiment (one year). Groups 7-11 (each 20 rats) were given a test chemical corresponding to Groups 2-6, respectively. Group 12 (20 rats) served as a control. The incidence and average number of intestinal tumors in Group 2 (47%, 0.57 +/- 0.68) were significantly less than in Group 1 (74%, 1.07 +/- 0.87) (P < 0.05, respectively). Multiplicity of intestinal neoplasms of Group 3 (0.55 +/- 0.60) or 4 (0.47 +/- 0.51) was also significantly smaller than that of Group 1 (P < 0.05 and P < 0.01, respectively). These results suggest that flavoglaucin, shikonin and gingerol might be promising chemopreventive agents for intestinal neoplasia.

The number of silver-stained nucleolar proteins (AgNORs) was enumerated in preneoplastic and neoplastic rat tongue lesions induced by 4-nitroquinoline 1-oxide (4-NQO). Male ACI/N rats were given 0 to 10 p.p.m. 4-NQO for 12, 20 or 36 weeks to induce hyperplasia, dysplasia and neoplasm in tongue. The mean numbers of AgNORs stained by a modified one-step silver colloid method in various epithelial lesions were as follows: normal squamous epithelium (n = 5), 1.52 +/- 0.03; non-lesional squamous epithelium (n = 5), 1.58 +/- 0.04; hyperplasia (n = 20), 1.84 +/- 0.15; dysplasia (n = 20), 2.32 +/- 0.12; papilloma (n = 6), 2.23 +/- 0.10; and squamous cell carcinoma (n = 4), 3.06 +/- 0.26. Thus, the mean number of AgNORs showed a stepwise increase from untreated and treated, histologically normal squamous epithelium through hyperplasia and dysplasia to squamous cell papilloma and carcinoma, although the value of severe dysplasia was between those of papilloma and carcinoma. These results indicate that the mean number of AgNORs may reflect the proliferative nature of tongue lesions, as suggested in carcinogenesis of other organs, and also suggest that severe dysplasia is a direct precursor lesion for squamous cell carcinoma of the tongue induced by 4-NQO.

The expression of cytokines, TNF-alpha and IL-1 alpha, was examined by means of a reverse transcription followed by PCR (RT-PCR) in rat colon carcinogenesis. Forty male F344 rats were used and divided into four groups. At the start of the experiment, 20 rats were treated with methylazoxymethanol (MAM) acetate (25 mg/kg body wt, one time, i.p.) and divided into two groups; group 1 was exposed to 1% 1-hydroxyanthraquinone (1-HAQ) and group 2 was fed a basal diet during the experiment (40 weeks). Other rats were also divided into two groups; group 3 was exposed to 1% 1-HAQ as group 1, and group 4 was used as control. Tumor incidence (100%) and multiplicity (5.00 +/- 2.05) in group 1 were significantly greater than those in group 2 (20% and 0.2 +/- 0.42) and group 3 (10% and 0.10 +/- 0.32) (P < 0.01 and P < 0.01 respectively). RT-PCR technique with RNA was applied to the tissues from colon neoplasms and mucosa in each group. Expression of TNF-alpha and IL-1 alpha in the colon neoplasms was much stronger than that in the colon mucosa of each group (P < 0.001 and P < 0.01 respectively). The expression of TNF-alpha was more remarkable in the colon mucosa of group 1 than that in corresponding tissue of groups 2 and 3 (P < 0.01). The expressions of TNF-alpha and IL-1 alpha were more increased in the colon mucosa of groups 1, 2 and 3 than that in group 4 as control (P < 0.01 and P < 0.05 respectively). The results indicate that TNF-alpha and IL-1 alpha may act as growth factors in rat colon carcinogenesis by MAM acetate and 1-HAQ. In addition, the synergistic effect of 1-HAQ with MAM acetate in colon carcinogenesis might be related to biological effects of the cytokines expressed in the inflammatory condition generated by 1-HAQ.