Coexpression of Multiple Sertoli Cell and Leydig Cell Marker Genes in the Spontaneous Testicular Tumor of F344 Rat: Evidence for Phenotypical Bifurcation of the Interstitial Cell Tumor

The development of testicular tumor has been frequently observed in some laboratory rat strains. In the present study, we have further characterized the testicular tumor that spontaneously develops in the F344 rat (F344/Jcl). Tumor cells first appeared in the interstitium and developed into multifocal nodular lesions. In the later stage, the whole testes were occupied by tumor cells that consisted of three different types of cells in morphological appearance: large clear type, small eosinophilic type and intermediate type. To determine the character of these cells, we examined the expression of marker genes for Sertoli cells (e.g., transferrin) and Leydig cells (e.g., 3β–hydroxysteroid dehydrogenase 1 (3β–HSD 1)). Transferrin and 3β–HSD 1 mRNAs were found in all 8 tumor samples analyzed hy northern blotting. By in situ hybridization, we observed a substantial amount of 3β–HSD 1 mRNA and little or no transferrin mRNA in the large clear cells. In contrast, the small eosinophilic cells showed little or no 3β–HSD 1 mRNA and a large amount of transferrin mRNA, suggesting that the tumor was a mixture of at least two types of cells. Other Sertoli cell marker genes, such as cyclic protein 2 and sulfated glycoprotein 2, were expressed in all 8 tumors analyzed, and testin and steel factor (SLF), the c–kit receptor ligand, were also expressed in some of the tumors (testin, 75%; SLF, 25%), while other Leydig cell markers, LH receptor and c– kit , were expressed in 87% and 80% of the tumors, respectively. These results indicate that the spontaneous testicular tumor of F344 rat is of interstitium origin, showing phenotypical bifurcation possibly via transdifferentiation.     

Enhancement of Tumorigenicity and Invasion Capacity of Rat Mammary Adenocarcinoma Cells by Epidermal Growth Factor and Transforming Growth Factor-β

We have studied the effects of growth factors and cytokines on the tumorigenicity and invasion capacity of tumor cells by using regressor and progressor tumor cell lines (ER-1 and ERpP, respectively) derived from an SHR rat mammary adenocarcinoma. ER-1 cells regress spontaneously whereas ERpP cells show invasive growth and high metastasis to lung and other organs in syngeneic SHR rats. When ER-1 cells were pretreated with either epidermal growth factor (EGF) or transforming growth factor-β (TGF-β) for 24 h in vitro , and intraperitoneally transplanted into SHR rats, they grew and killed the host, whereas ER-1 cells pretreated with tumor necrosis factor-α did not. Tumorigenicity and invasion capacity of ERpP cells were also enhanced by treatment with EGF and TGF-β. The ER-1 cells pretreated with EGF, once grown in vivo , had acquired irreversible tumorigenicity and invasion capacity without requiring further EGF treatment, and the enhanced malignancy was irreversible. These findings suggest that growth factors play an important role in acquisition of malignancy of tumor cells.     

A model of overall regulation of body fluids

A large-scale model of body fluid regulation was presented for the purpose of studying problems concerning body fluid disturbances and fluid therapy. This model, containing subsystems of circulation, respiration, renal function, and intra and extracellular fluid spaces, was described mathematically as a set of nonlinear differential and algebraic equations of more than 200 variables. A special feature is that the respiratory and renal subsystems are combined into one system, so that acid-base disturbances of body fluid can be simulated over a wide range of time scales. Behavior of the model for various kinds of inputs simulated with a digital computer was in good agreement with a number of experimental results pertaining to body fluid and acid-base disorders. The model presented in this paper is considered to have good applicability to some clinical problems and to be a useful framework for physiological experimental research.     

Suppression of glutathione S-transferase placental form-positive foci development in rat hepatocarcinogenesis by Chlorella pyrenoidosa

The modifying effects of dietary administration of dried Chlorella pyrenoidosa powder (C. pyrenoidosa) on the development of glutathione S-transferase placental form-positive foci (GST-P-positive foci), which are putative preneoplastic lesions, in male F344 rats were investigated using a medium-term liver bioassay system. In rats given 10% C. pyrenoidosa in a basal diet, the number and area of GST-P-positive foci in the rat livers, which diethylnitrosamine (DEN) initiated and 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx) promoted, were significantly decreased compared with those fed a basal diet not containing C. pyrenoidosa. The inhibition percentage of the number and area of GST-P-positive foci > or =0.2 mm in diameter was 67.6 and 74.2%, respectively (p<0.01). Furthermore, C. pyrenoidosa significantly decreased the number of GST-P-positive foci induced by MeIQx alone. The inhibition percentage of the number of GST-P-positive foci <0.2 mm in diameter was 52% (p<0.01). These results suggest that C. pyrenoidosa has chemopreventive effects against hepatocarcinogenesis in rats. C. pyrenoidosa appears to be a promising chemopreventive agent for human liver neoplasia and carcinogenesis induced by heterocyclic amines such as MeIQx.     

Complex formations involving both SP-1 and SP-3 at the transcriptional regulatory sequence correlate with the activation of the Keratin 14 gene in human oral squamous cell carcinoma cells

We have previously reported that significantly higher levels of Keratin 14 (Ker-14) was observed in oral squamous cell carcinoma (OSCC) and severely dysplastic tissues, whereas this expression was reversed in hyperplasia and in mild to moderate dysplasia. In this study, the mechanism of Keratin 14 activation in oral squamous cell carcinoma (OSCC) cell lines (HSC-2, HSC-3 and Ca9-22) was investigated. Reporter analysis demonstrated that an upstream region (-1759/-1629) accounted for efficient promoter activity. Furthermore, electromobility sift and supershift assay demonstrated that interactions of the SP-1/SP-3 complex at the elements resided in -1737/-1702 and -1680/-1652 and may be essential for this activation in OSCC cells.     

A case report of bladder hernia associated with prostate cancer

We report a case of bladder hernia. A 68-year-old man was admitted to our hospital for the management of prostate cancer. An egg-sized soft mass was palpated at his right inguinal region. Magnetic resonance imaging and cystography revealed that the mass was a bladder hernia. During radical prostatectomy, we had to resect the bladder hernia for safe regional lymphadenectomy. This hernia was the extraperitoneal type. The stage of prostate cancer was pT3b N0 M0. This is the third reported case of inguinal bladder hernia associated with prostate cancer in Japan.