[Surgically treated desmoid tumor of the chest wall which located at the previous thoracotomy site].

Desmoid tumor is a soft-tissue tumor of unknown cause. Since recurrence sometimes occurs even with complete resection, careful consideration of which portions to resect and close postoperative followup are recommended. Seventeen months after undergoing a right upper lobectomy for primary lung adenocarcinoma, a 65-year-old female patient experienced pleural tumor which located at the previous thoracotomy site, as revealed by chest X-ray and computed tomography (CT). While needle aspiration biopsy revealed no malignancy, recurrence of the cancer could not be ruled out clinically. The tumor was resected with chest wall and lung and the histopathological diagnosis was desmoid tumor. This case demonstrates the importance of conducting differential diagnosis with recurrence or desmoid tumor after operation to treat lung cancer. Five years after resection of the desmoid tumor, no recurrence is observed.

Purple corn color suppresses Ras protein level and inhibits 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in the rat.

Anthocyanins belong to the class of phenolic compounds collectively named flavonoids. Many anthocyanins are reported to have inhibitory effects on carcinogenesis. Purple corn color (PCC), an anthocyanin containing extract of purple corn seeds, is used as a food colorant. The major anthocyanin in PCC is cyanidin 3-O-beta-D-glucoside (C3-G). The present study was conducted to assess the influence of dietary PCC on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in rats. PCC significantly inhibited DMBA-induced mammary carcinogenesis in human c-Ha-ras proto-oncogene transgenic (Hras128) rats and in their non-transgenic counterparts. PCC and C3-G also inhibited cell viability and induced apoptosis in mammary tumor cells derived from Hras128 rat mammary carcinomas. At the molecular level, PCC and C3-G treatment resulted in a preferential activation of caspase-3 and reduction of Ras protein levels in tumor cells. It is proposed that C3-G could act as a chemopreventive and possibly chemotherapeutic agent for cancers with mutations in ras. Secondly, the in vitro-in vivo system used in this study can be utilized for screening for cancer preventive compounds that act via Ras down-regulation.

Possible application of human c-Ha-ras proto-oncogene transgenic rats in a medium-term bioassay model for carcinogens.

With the aim of developing a medium-term assay for screening of environmental carcinogens, we exposed mammary carcinogen sensitive human c-Ha-ras proto-oncogene transgenic (Hras128) rats to various carcinogens, including compounds that do not normally induce mammary tumors. Seven-week-old Hras128 rats and wild-type littermates received administrations of 3-methylcholanthrene (3-MC), benzo[a]pyrene (B[a]P), anthracene, pyrene, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), dimethylarsinic acid (DMA), diethylnitrosamine (DEN) or azoxymethane (AOM) and were sacrificed at week 12 (females) (at week 10 for the 3-MC group) or week 20 (males). Female Hras128 rats receiving NNK, DEN, or DMA showed a significant increase in mammary tumor incidence and/or multiplicity compared to the respective values with olive oil or deionized distilled water (DDW) vehicles. In male Hras128 rats, a significant increase in mammary tumors was also observed in groups administered 3-MC, B[a]P, anthracene, IQ, and NNK. Mutations of transgenes were observed in codons 12 and/or 61 in the induced tumors by PCR-RFLP except in the DEN group in female and in the MeIQx group in male Hras128 rats. Thus various carcinogens, not necessarily limited to those normally targeting the breast, were found to induce mammary carcinomas in Hras128 rats, especially in females, pointing to potential use for medium-term screening.

Possible enhancing activity of diacylglycerol on 4-nitroquinoline 1-oxide induced carcinogenesis of the tongue in human c-Ha-ras proto-oncogene transgenic rats.

1,2-diacylglycerol (1,2-DAG) is involved in cell proliferation as an activator of protein kinase C (PKC) and has been shown to stimulate growth of cancer cells, raising the possibility of a role in tumor promotion. Ingested DAG oil, containing 70% 1,3-DAG and 30% 1,2-DAG, is digested and considered to be safe as edible oil. However, DAG may directly contact with oral cavity mucosa in undigested form. The present study was conducted to examine the effects of DAG oil on carcinogenesis in c-Ha-ras proto-oncogene transgenic (Tg) rats administered 4-nitroquinoline 1-oxide (4NQO, 10 ppm) in their drinking water for 10 weeks for initiation of mainly upper digestive organs. DAG oil added in basal diet at 5.5%, 2.75%, 1.38% and 0% with total fat made up to 5.5% with triacylglycerol (TAG) was administered during the initiation and post-initiation period. The study was terminated at week 12 (Tg females) and 20 (Tg males, wild females and males). The fatty acid composition of DAG oil was similar to TAG (linoleic acid 46.6% and oleic acid 38.9%). In Tg male rats, DAG oil administration was associated with significant increase (P<0.05) in the incidence of squamous cell carcinomas (SCC) of the tongue (5.5% DAG, 43.8%; 2.75% DAG, 20%; 1.38% DAG, 14.3%; 0%, 12.3%) with the Cochran-Armitage trend test and also number of tumors in coefficients for linear contrast trend tests. Tongue SCC induction of wild males and all females was not significant. The present results suggest that DAG oil may have enhancing and/or promotion potential for tongue carcinogenesis in male Tg featuring elevated ras expression.

High susceptibility of human c-Ha-ras proto-oncogene transgenic rats to carcinogenesis: a cancer-prone animal model.

Transgenic animals carrying human c-Ha-ras proto-oncogene, v-Ha-ras transgenic mice, pim-1 transgenic mice and several knockout mice deficient of tumor suppressor genes, such as p53, have been shown to exhibit increased carcinogen susceptibility. As a result, studies into practical application and medium-term screening of environmental carcinogens are under way. Given the advantages of rat models characterized by larger organ size, abundant information regarding preneoplasias and virus-free constitution, we have concentrated on the generation of transgenic rats bearing copies of the human c-Ha-ras proto-oncogene and shown the Hras128 strain to be extremely sensitive to the induction of mammary carcinomas, and to a lesser extent, lesions in the urinary bladder, esophagus and skin. In most, if not all, the mammary cancers mutations of the transgene but not the endogenous H-ras gene are present, appearing to occur early in the process of tumorigenesis, which involves proliferation of cells in TEB and intraductal hyperplasia before carcinomas arise. Preliminary findings suggest that this is independent of endogenous ovarian hormones, although inhibited by soy isoflavones and promoted by atrazine and nonylphenols. Although further studies of the mechanisms are clearly necessary, the model appears to have great potential for screening purposes, not only for modifiers active in the breast, but also other organs where tumors characterized by ras gene mutations develop.

Cancer prevention by natural compounds.

Increasing attention is being paid to the possibility of applying cancer chemopreventive agents for individuals at high risk of neoplastic development. For this purpose by natural compounds have practical advantages with regard to availability, suitability for oral application, regulatory approval and mechanisms of action. Candidate substances such as phytochemicals present in foods and their derivatives have been identified by a combination of epidemiological and experimental studies. Plant constituents include vitamin derivatives, phenolic and flavonoid agents, organic sulfur compounds, isothiocyanates, curcumins, fatty acids and d-limonene. Examples of compounds from animals are unsaturated fatty acids and lactoferrin. Recent studies have indicated that mechanisms underlying chemopreventive potential may be combinations of anti-oxidant, anti-inflammatory, immune-enhancing, and anti-hormone effects, with modification of drug-metabolizing enzymes, influence on the cell cycle and cell differentiation, induction of apoptosis and suppression of proliferation and angiogenesis playing roles in the initiation and secondary modification stages of neoplastic development. Accordingly, natural agents are advantageous for application to humans because of their combined mild mechanism. Here we review naturally occurring compounds useful for cancer chemprevention based on in vivo studies with reference to their structures, sources and mechanisms of action.