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High expression of the proliferation and apoptosis associated CSE1L/CAS gene in hepatitis and liver neoplasms: correlation with tumor progression.

The CSE1L/CAS protein (CAS) is a Ran-binding protein with a function as nuclear transport (export) factor. Like recently observed for ran and other ran-binding proteins, CSE1L/CAS simultaneously plays a role in the mitotic spindle checkpoint, which assures genomic stability during cell division. This checkpoint is frequently disturbed in neoplasias of various origin, including hepatic tumors. We have evaluated by immunohistology the expression of CAS in adult and embryonic liver, hepatitis, and in liver hyperplasias. Normal hepatocytes revealed no CAS expression while embryonic liver showed strong expression in all parenchymal cells. Bile ducts stained positive with anti-CAS antibodies, and strong CAS expression was also detected at the interface between bile ducts and hepatocytes under conditions associated with regenerative proliferation. The localization of these CAS expressing cells correlated with the distribution of putative liver stem-cells. In active viral (but not in inactive) hepatitis, strong hepatocytal CAS expression correlates in site and intensity with degree of inflammation. Neoplastic liver demonstrated different degrees of CAS expression: no remarkable expression in adenomas, moderate expression in a narrow rim of hepatocytes and in periseptal cholangiolar proliferations in focal nodular hyperplasia, and strong CAS expression in hepatocellular carcinoma. Less differentiated tumors stain stronger than well differentiated. Cholangio-cellular carcinomas show even stronger CAS expression than hepatocellular carcinomas. Our observation of strong expression of CAS in liver cells that are committed for proliferation among them possibly liver stem cells, and in liver neoplasms, is consistant with the fact that CAS functions not solely as a nuclear transport factor but that it is also essential for cell proliferation, particularly for the mitotic spindle checkpoint. Interestingly, genomic instability is frequently observed in hepatic tumors which we have shown here to express large amounts of CAS. Since the degree of CAS-expression correlates with the grade of tumor dedifferentiation, we suggest that CAS should also be further investigated as prognostic marker for hepatic neoplasms.

Adult↗

Field and laboratory studies of the etiology of liver neoplasms in marine fish from Puget Sound.

A series of field studies was conducted between 1979 and 1985 in Puget Sound, Washington State, to investigate etiological relationships between prevalences of hepatic neoplasms in bottom-dwelling marine fish species, with emphasis on English sole (Parophrys vetulus), and concentrations of toxic chemicals in sediments and affected fish. Statistically significant (p less than or equal to 0.05) correlations have been found between the prevalences of hepatic neoplasms in English sole and the following parameters: sediment concentrations of aromatic hydrocarbons, and concentrations of the metabolites of aromatic compounds in the bile of affected sole. A significant difference (p less than 0.001) was also found between the relative concentrations of aromatic free radicals in the liver microsomes of English sole with liver lesions compared to sole without liver lesions. Laboratory studies designed to evaluate the etiology of the liver neoplasms in English sole have also yielded evidence that is consistent with the view that high molecular weight aromatic hydrocarbons, e.g., benzo[a]pyrene (BaP), are hepatocarcinogens in English sole. The current status of a series of long-term (up to 18 months) exposures of English sole and rainbow trout (Salmo gairdneri) to selected fractions of Puget Sound sediment extracts, enriched with aromatic hydrocarbons and nitrogen-containing aromatic compounds, and to individual carcinogens (e.g., BaP) is discussed.

Animals↗

Pathogenesis of skin and liver neoplasms in white suckers from industrially polluted areas in Lake Ontario.

Increased prevalences of epidermal and hepatobiliary neoplasms in white suckers (Catostomu commersoni) and brown bullheads (Ictalurus nebulosus) in the Western region of Lake Ontario have been associated with industrial pollution, but the identity and causative role of environmental carcinogens have not yet been established. Most epidermal tumors of lip and body skin are benign focal proliferations that occur in fish from the polluted Hamilton region, and also in fish from less polluted sites in the Great Lakes. These skin tumors in white suckers do not have consistent alterations in cellular glutathione S-transferases (GST), suggesting that growth of skin tumors is not promoted by chemicals normally detoxified by GST. However, elevated levels of glutathione peroxidase (GPO) and glutathione reductase (GR) in skin papillomas are indicative of promotional peroxidative tissue injury, either caused directly by xenobiotics or indirectly by chemical-induced inflammation. Liver tumors in white suckers from Lake Ontario include preneoplastic, benign, and malignant populations of hepatocellular and biliary cells, all of which are more prevalent in fish from polluted sites. These liver tumors are consistently associated with chronic cholangiohepatitis and segmental cholangiofibrosis, but these conditions also occur in white suckers in non-industrial locations. Thus, the natural occurrence of biliary disease, not attributable to industrial pollution, may have some influence on the development of liver tumors. Some preneoplastic lesions and the majority of neoplastic hepatocellular and biliary lesions in white suckers have low levels of total GST, indicating that these liver neoplasms are not promoted by xenobiotics normally detoxified by hepatic GSTs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Spontaneous hemorrhage in liver neoplasms. Experience at an institution].

OBJECTIVE: Retrospective review of a single Institution experience with the management of hepatic neoplasms complicated with spontaneous bleeding. METHODS: In a 11 years period from 1980 to 1990 we reviewed the medical charts of patients treated at our Institution with the diagnosis of hepatic neoplasms complicated with sudden bleeding. We recorded demographic information, clinical manifestations, treatment and outcome. A review of the world literature was done. RESULTS: We found six patients with the diagnosis of liver tumors complicated with sudden bleeding. Five patients were female with a age range from 30 to 67 years old. Four of them had an adenoma (three of them single and one multiple) and the fifth had a non-parasitic cyst. Seventy-five per cent of the patients with the diagnosis of adenoma had used in the past oral contraceptives for at least three years. The sixth patient was a male with a ruptured hepatocellular carcinoma. Three patients were admitted in shock. Successful transcatheter hepatic arterial embolization was performed in two patients; the third required operative hemostasis. Major hepatic resections were performed in three patients including a total hepatectomy and liver transplant. All patients recovered satisfactorily. CONCLUSIONS: The spontaneous rupture of benign and malignant tumors of the liver is not a common phenomenon, but is a serious complication. The experience of our Institution and the reports of literature favor CT scan and arteriogram as the most effective diagnostic methods in this group of patients, but arteriogram has the advantage of its therapeutic potential. The long term prognosis of this patients depends of their pathological diagnosis.

Adenoma↗

Percutaneous radiofrequency ablation for the treatment of liver neoplasms in the caudate lobe left of the vena cava: electrode placement through the left lobe of the liver under CT-fluoroscopic guidance.

Five hepatocellular carcinomas and one liver metastasis located in the caudate lobe left of the inferior vena cava were successfully treated by radiofrequency (RF) ablation by placing the RF electrode into each tumor through the left lobe of the liver under the CT-fluoroscopic guidance. All tumors were free of enhancement on dynamic contrast-enhanced CT during the mean follow-up period of 6.3 months. There were no major complications related to the procedures.

Aged↗