Takuji Tanaka

Induction of hepatic peroxisome proliferation in mice by lactofen, a diphenyl ether herbicide

A technical grade of lactofen (1[carboethoxy]ethyl 5-[2-chloro-4-[trifluoro-methyl] phenoxy]-2-nitrobenzoate) has been shown to induce liver tumors in mice. To determine a possible mechanism of action, the effect of exposure for 7 weeks to dietary concentrations of 2, 10, 50, and 250 ppm technical grade lactofen and 250 ppm of pure lactofen was studied for various liver parameters in groups of male and female CD-1 mice. Liver-weight to body-weight ratio, liver catalase, liver acyl-CoA oxidase, liver cell cytoplasmic eosinophilia, nuclear and cellular size, and peroxisomal staining were increased by the tumorigenic dose of lactofen, i.e., 250 ppm, in a fashion similar to the comparison chemical nafenopin (500 ppm), which is a peroxisome proliferator. Lower doses of lactofen that were reported as nontumorigenic had little or no effect on these parameters. Thus, pure and technical grade lactofen appear to induce murine liver tumors through a mechanism similar to epigenetic hepatocarcinogens of the peroxisome proliferating type.

Morphologic and Cytochemical Properties of Mouse liver Neoplasms Induced .- by Diethylnitrosamine and Promoted by 4,4'-Dichlorodiphenyltrichloroethane, Chlordane, or Heptachlor

The relationships between the gross appearance, histologic types, and cytochemical characteristics of hepatocellular neoplasms were studied in B6C3F1 mice given the liver carcinogen diethylnitrosamine either alone or followed by the organochlorine pesticides, 4,4-dichlorodiphenyltrichloroethane, chlordane, or heptachlor as promoting agents. Hepatocellular neoplasms were categorized according to their cytoplasmic staining properties with hematoxylin and eosin. Acidophilic neoplasms more of ten displayed increased activity of alkaline phosphatase than did basophilic neoplasms. The activities of glucose-6-phosphatase and adenosine triphosphatase were decreased in both acidophilic and basophilic neoplasms. There was no difference in the activities of these enzymes or γ-glutamyltranspeptidase between adenomas and carcinomas, although most neoplasms did not display γ-glutamyltranspeptidase. Chlordane or heptachlor exposure increased the alkaline phosphatase activity in neoplastic cells, but not that of other enzymes. The majority of neoplasms displayed a deficiency of iron accumulation. The macroscopic appearance of neoplasms was closely related to their cytoplasmic staining properties and cytochemical characteristics.

Recent advances in pathobiology and histopathological diagnosis of inflammatory bowel disease

Abstract nIn order to make a diagnosis of ulcerative colitis (UC) or Crohns disease (CD) which belongs to inflammatory bowel disease (IBD), it is important to evaluate pathologic material in conjunction with clinical, laboratory and

Glutathione S-Transferase Placental Form in Human and Rat Gliomas and Its Possible Role in Drug Resistance

Glutathione S-transferases (GSTs) are an important family of the detoxifying enzymes catalyzing the conjugation of glutathione to a wide variety of hydrophobic electrophilic substances [1]. GSTs have various isoenzymes which have been studied extensively in rats [2]. The isozyme, rat placental form (GST-P) has been shown to be a marker for preneoplastic or neoplastic lesions in chemical hepatocarcinogenesis [3], GST-P is well recognized to exist in normal rat astrocytes, and is regarded as a major form of isozymes expressed in rat brain [4]. GST-P is expressed in GST-P-negative rat glioma cells after induction of benign transformation by dibutyryladenosine 3′,5′-cyclic monophosphate [5]. The human placental form of GST (GST-π), which is closely related to GST-P immunologically, is also contained in normal human astrocytes. It may be that the GST-π; or GST-P contained in normal astrocytes is concerned with the detoxifying function against xenobiotics for the protection of neurons from their toxic effects. We have already demonstrated the expression of GST-π in human gliomas [6].

Activity of the anorectic agent 1,3-bis[2-cyano-5-(trifluoromethyl)-phenyl]triazene in in vitro and in vivo liver promoting assays

A substituted 1,3-diaryltriazene, 1,3-bis[2-cyano-5-(trifluoromethyl)phenyl]triazene (BPT), was studied for promoting activity in vitro and in vivo. BPT inhibited intercellular molecular exchange between cultured hepatocytes and rat liver epithelial cells, although the effect was not consistent. For the in vivo assay, male F344 rats were first exposed to N-2-fluorenylacetamide (FAA) for 8 weeks to induce liver altered foci, after which those maintained on control diet for an additional 12 weeks developed a 33% incidence of liver neoplasms. In rats given 0.02% BPT in the diet as a second exposure, the final incidence of liver neoplasms was 92%, which was comparable to the enhancement by phenobarbital (PB), a known liver neoplasm promoter. In the rats given BPT after FAA, the area occupied by gamma-glutamyltranspeptidase (GGT)-positive preneoplastic and neoplastic lesions was significantly higher than in the rats exposed to FAA only. Feeding of BPT alone for 12 weeks did not induce either liver altered foci or neoplasms and it was non-genotoxic in the hepatocyte DNA repair test. Therefore, although additional studies are needed to firmly establish the basis for the enhancement of liver carcinogenesis, BPT is suggested to be a new type of liver neoplasm promoter.

Primary adenoid cystic carcinoma in the peripheral lung: a cytological, histopathological and immunohistochemical report of two cases

Primary adenoid cystic carcinoma (ACC) of the peripheral lung is a rare entity. Here we report two cases of primary ACC. Case 1 is an 84-year-old male with a past-medical history of cecal cancer presented with a 10 mm left upper lung nodule. Case 2 is a 40-year-old female who presented with 30 mm right upper lobe. Intraoperative (Case 1) and pre-operative (Case 2) histopathologic and cytologic diagnoses were consistent with a primary peripheral lung ACC. An upper lobectomy±mediastinal lymph node dissection was performed and immunohistochemical staining with thyroid transcription factor (TTF)-1, c-KIT and MYB on the excision specimen confirmed our diagnosis.

Preneoplasia and carcinogenesis of the oral cavity

Abstract nOral cancer, ranking sixth in the cancer incidence worldwide, is one of the most common neoplasms. Preneoplastic or premalignant (precancerous) lesions are lesions that can potentially transform into malignancy in a variety of

Primary malignant melanoma of the female urethra: a rare case of cytological observation

We herein report a rare case of primary malignant urethral melanoma developed in an elderly Japanese patient with hypertension, diabetes and hyperlipidemia. An 80-year-old female presented at our hospital with a history of urodynia and perineal pain lasting for several months. Cystoscopy revealed cystitis and urethritis with erosion. At that time, urinary cytology was negative for malignancy, although melanophages were observed. Four months later, lower abdominal computed tomography and magnetic resonance imaging indicated urethral tumors. Urinary cytology subsequently detected malignant melanoma, and a biopsy of the urethra confirmed malignancy. Although inguinal lymph node metastasis was found 16 months postoperatively, the patient has remained free of disease for more than six years after surgery and chemotherapy.

Androgenic adult granulosa cell tumor with secondary amenorrhea and elevated luteinizing hormone

Abstract nGranulosa cell tumors (GCTs), adult type, are the most common type of ovarian sex cord tumors. Menstrual irregularity, even secondary amenorrhea is frequently observed in premenopausal women bearing GCTs with hormonal activity.

The Stem Cells in Liver Cancers and the Controversies

Abstract Liver bipotential stem/progenitor cells can give rise to both hepatocytes and cholangiocytes. These cells might also be potential sources of liver cancers, such as hepatocellular carcionoma (HCC) and cholangiocarcinoma (CCA), and both are heterogeneous malignancies. Further, combined HCC-intrahepatic CCA, a form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation, has also been reported, supporting the existence of bipotent cancer stem cells in liver. HCC, CCA, and HCC-intrahepatic CCA are heterogeneous in the diagnosis by immunohistochemistry and include a subset of cells expressing various stem cell markers. In this chapter, we summarize the current knowledge of stem cells in normal liver and liver cancers and discuss the controversial points.