Primary hepatoma

As with many enzymes the role of AMP aminohydrolase in the hierarchy of metabolic catalysts is not clearly understood. Enzymic activity in muscle is markedly reduced in the dystrophic mouse (161, 162), in humans suffering from Duchanne type muscular dystrophy (163), in hypokaliemic periodic paralysis (164), and upon denervation of normal and dystrophic mouse gastronemii (165). Activity is reported to increase in both transplanted and primary hepatomas (151) and in precancerous livers prior to the onset of neoplasia induced by feeding or by intraabdominal injections of the potent carcinogen 3 -methyl-4-dimethyl-aminoazobenzene (166). The weak carcinogen, 4 -methyl-4-dimethyl-aminoazobenzene was not effective (166). Increases in enzyme activity concomitant with altered nuclear-nucleolar morphology, nuclear RNA content, and nuclear RNA biosynthesis were also observed after injections of thioacetamide, a hepatocarcinogen (167, 168). 

The concentration of acid mucopolysaccharides in serum, and their excretion in urine, are increased in patients with rheumatoid arthritis (D7), lupus erythematosus (D6), diabetes (C7), and leukemia (R2, SIO) and other malignant diseases (R2). The daily urinary excretion of acid mucopolysaccharides was within the normal range in cases of acute hepatitis, but was usually increased in chronic hepatitis and in florid cirrhosis (K5). A decrease in the amount of acid mucopolysaccharides excreted was found in primary hepatoma, whereas in most cases of obstructive jaundice the amount was markedly increased (K5). 

Mn-SOD Levels in Primary Hepatoma and Primary Biliary Cirrhosis... 

Approximately 60% of the patients with primary hepatoma gave positive values for Mn-SOD in the ELISA. Because serum Mn-SOD levels were also elevated in various other diseases, including gastric cancer and primary biliary cirrhosis, however, whether the immunoreactive Mn-SOD can be used as a marker for the diagnosis and monitoring of primary hepatoma remains to be clarified. 

The urinary excretion of glycosaminoglycans by juvenile cases of vitamin A deficiency and of protein-calorie malnutrition (kwashiorkor) is less than normal (M41). The predominant differences are the absence of hyaluronic acid and the presence of chondroitin sulfate of low sulfate content (C12). Treatment of the cases with vitamin A deficiency restored the glycosaminoglycan spectrum to normal. Decreased urinary glycosaminoglycan levels have also been noted in primary hepatoma (K6). It has been suggested that the urinary excretion pattern of individual glycosaminoglycans is pathognomic of certain hereditary bone diseases (T3). 

Phase I/II trials were conducted in 31 patients of which 23 had primary hepatoma [85] and the compound was given by intravenous infusion... 

Thus far, the EPR effect has been credited for the clinical development of SMANCS and the pHPMA-doxombicin conjugate (PKl) For example, arterially administered SMANCS in patients with primary hepatoma displayed tumor/blood ratios as great as 2000 when combined with Lipidol as carrier Furthermore, the clinical trials ofPKl suggested that this dmg displayed antitumour activity in chemotherapy-refractory patients, considerably reduced toxicity compared with doxombicin, and provided evidence of tumor-selective targeting... 

Treatment of primary hepatoma by the SMANCS/Lipiodol method has been approved in Japan for more than 6 years, since 1995. When the drug is dehvered by intraarterial administration using catheter, this treatment produces definite tumor size reduction (in >90% of cases), improved survival scores, and especially a good quality of life with very little side effect (Table 4). Furthermore, patients can be out of bed within a few days after the procedure (the Seldinger method is used for arterial infusion under the X-ray system). For all cases of primary hepatoma combined (including Child s criteria of A-C cirrhosis), the 5- to 7- year survival rate is about 30% with this method. With other treatments, no survival would be expected during this time frame. Hepatoma patients with milder liver cirrhosis (such... 

A similar approach has been used more recently by Miyata et al (2006) to prepare tumour marker-responsive hydrogels. These polymeric networks, prepared by biomolecular imprinting, were conjugated with lectins and antibodies so that they exhibited volume changes in response to antifreeze glycoprotein (AFP), a glycoprotein which is widely used for the serum diagnosis of primary hepatoma. 

Strictly speaking these are tests which measure the specific functions of the liver, e.g. its excretory functions (bilirubin, BSP etc.) or its synthetic function (as reflected by serum albumin levels). In practice the term is also used to include tests for liver cell damage (e.g. aminotransferases released from damaged cells), tests for cholestasis (e.g. alkaline phosphatase and 5 -nucleo-tidase) and possibly a number of other miscellaneous tests (e.g. a-fetoprotein for primary hepatoma). 

Substances produced by a tumour which are normally only produced by embryonic cells, e.g. a-fetoprotein in primary hepatoma, and carcinoembryonic antigen in cancers of the gastrointestinal tract. 

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