Promyelocytic leukemia protein (PML) is a major component of PML nuclear bodies (PML NBs). Fusion of promyelocytic leukemia gene (PML) with retinoic acid receptor alpha gene with the t (15;17) translocation causes disassembly of PML NBs, leading to development of acute promyelocytic leukemia. In contrast, PML overexpression as well as different morphological changes of PML NBs were described in a few solid tumors. In this study, the expression of PML through the multistep hepatocarcinogenesis was analyzed in 95 cases of human hepatocellular carcinomas (HCCs) for comparison along with dysplastic nodules (DNs) and background liver cirrhosis (LC) or chronic hepatitis by immunohistochemistry and immunoblot. In addition, cases of HCCs were further evaluated according to their histologic grade and etiology. The amount of PML as well as the num-ber and size of PML NBs increased gradually through the progression from LC, DNs to HCCs. The overexpression of PML in HCCs was much more closely associated with HBV infection than HCV infection or alcoholic liver disease. The PML expression, however, was not correlated with histologic grade of HCCs. These results suggest that PML is involved in the early stage of multistep hepatocarcinogenesis, and HBV infection may be associated with the overexpression of PML and the morphological alteration of PML NBs.
Carcinoma, Hepatocellular/*chemistry/ultrastructure ; Cell Nucleus/*chemistry ; Human ; Liver/chemistry ; Liver Neoplasms/*chemistry/ultrastructure ; Neoplasm Proteins/*analysis ; Precancerous Conditions/*chemistry/ultrastructure ; Transcription Factors/*analysis ; Tumor Cells, Cultured

OBJECTIVETo study the physiopathologic basis of Weikangfu Granule (WKFG) in treating precancerosis of gastric mucosa in patients of chronic gastritis with Pi-deficiency syndrome (CG-PDS).

METHODSOne hundred and fifteen patients of CG-PDS who suffered from intestinal metaplasia (IM) and atypical hyperplasia (ATHP) of gastric mucosa, were divided into two groups. The treated group (n = 61) was treated by WKFG with its ingredients modified according to the syndrome type of patients. The control group (n = 54) was treated with Weishu granule. The histopathological and subcellular ultrastructural changes were detected by optical microscope, screening electronic microscope, transmission electronic microscope and histochemical staining; the nuclear and mitochondrial ultrastructure of gastric mucosa were analyzed with energy dispersion X-ray analyser and image analysis system. And the changes of cAMP, lipid peroxide (LPO), superoxide dismutase (SOD) before and after treatment in the treated group were measured and compared with those of the health control group consisting of 15 volunteers.

RESULTSThe symptomatic and pathological therapeutic effect in the treated group were significantly superior to those in the control group (P < 0.05). The contents of Zn, Cu, cAMP, SOD and (3)H-TdR LCT in gastric mucosa of the treated group before treatment were all lower than those of the healthy control group, yet all these indexes markedly increased after treatment, while serum LPO level, which increased before treatment was lowered after treatment. All the changes showed statistical significance (P < 0.05 or P < 0.01).

CONCLUSIONWKFG can reverse IM and ATHP in patients of CG-PDS, and the effect may be realized by way of increasing the level of Zn, Cu, cAMP and SOD in gastric mucosa, promoting cell differentiation, enhancing cellular immunity and reducing oxygen free radicals and lipid peroxidation.

Adult ; Aged ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Chronic Disease ; Copper ; analysis ; Cyclic AMP ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Gastric Mucosa ; chemistry ; pathology ; ultrastructure ; Gastritis, Atrophic ; pathology ; Humans ; Lipid Peroxides ; analysis ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Precancerous Conditions ; pathology ; Stomach Neoplasms ; pathology ; Superoxide Dismutase ; analysis ; Syndrome ; Yang Deficiency ; complications ; Zinc ; analysis