Docetaxel inhibits progression of human hepatoma cell line in vitro and is effective in advanced hepatocellular carcinoma

Background: Current chemotherapy for advanced hepatocellular carcinoma (HCC) is insufficient; only sorafenib has been proven to provide a modest survival benefit. A future direction of chemotherapy is to tailor treatment based on the chemosensitivity of each individual tumor. By doing so, only patients who stand to benefit from therapy will be exposed to potential side‐effects and morbidity. Although the use of docetaxel (DTX) for the treatment of lung, breast and gastric cancer has been reported, there are few reports about its use in the setting of HCC. Methods: To examine the efficacy of DTX for HCC, we established a human hepatoma cell line (TK cell) from the patient's malignant ascites from peritoneal carcinomatosis and treated it with DTX in vitro. Results: After we confirmed the efficacy of DTX in vitro, we treated our patient with DTX with positive results. Conclusion: In this study, we present a therapeutic approach by using DTX that supports the potential usefulness of personalized medicine in vitro and demonstrates it clinically.     

Effects of sucrose on plasma concentrations and urinary excretion of purine bases

To determine whether an increase in the plasma concentration of uric acid by sucrose intake is ascribable to enhanced purine degradation and/or decreased urinary excretion of uric acid, we measured the plasma concentrations of purine bases (uric acid, hypoxanthine, and xanthine) and uridine, as well as the urinary excretion of purine bases in 7 healthy subjects before and after administering sucrose at 1.5 g/kg of body weight in 2 related experiments, with and without an administration of 300 mg of allopurinol. In addition, in the control experiment without an administration of sugar and with an administration of 300 mg of allopurinol, we measured the same parameters in those 7 subjects. Without added allopurinol, sucrose increased the plasma concentration of uric acid by 11% (P<.01) as well as that of uridine, although it did not significantly increase the plasma concentrations of hypoxanthine and xanthine or the urinary excretion of uric acid. On the other hand, the plasma concentration and urinary excretion of hypoxanthine were increased by 2.4-fold (P<.05) and 3.42-fold (P<.05), respectively, and the plasma concentration of xanthine was increased by 1.2-fold (P<.05) together with an increase in the plasma concentration of uridine in the experiment with allopurinol administration. In contrast, the plasma concentration and urinary excretion of uric acid and the urinary excretion of xanthine were not increased. In addition, in the control experiment, all parameters did not change significantly. These results indicate that purine degradation enhanced by sucrose plays a major role in the increased plasma concentration of uric acid.     

Endocrine cells in ampullary carcinoma

Background/Purpose

As ampullary carcinoma originates from four anatomical regions, it may have different behaviors depending on its origin. We documented the presence of endocrine cells found in ampullary carcinoma, and we studied the clinicopathological implications of their presence.

Methods

We immunohistochemically examined the presence of an endocrine component in 62 surgically resected specimens of ampullary carcinoma, and we studied the clinicopathological differences between endocrine component-positive cases and endocrine component-negative cases.

Results

Endocrine cells were detected in 16 cases (26%); 11 cases had many endocrine cells, and five cases had scattered endocrine cells. Serotonin-positive cells were detected in all 16 cases, in which six cases had many positive cells. Several somatostatin-positive cells were detected in three cases. Endocrine cells were detected in ampulloduodenal polypoid lesions (two cases) and ampullopancreaticobiliary ducts (14 cases). The histology of 15 of the 16 endocrine component-positive ampullary carcinomas was the intestinal type. Pancreatic invasion and lymph node involvement were observed less frequently in endocrine component-positive cases (P < 0.01). There were no significant differences with respect to immunoreactivity for carbohydrate antigen (CA) 19.9, carcinembryonic antigen (CEA), and p53 overexpression, and K-ras mutations.

Conclusions

Endocrine component-positive ampullary carcinoma seemed to be derived from the ampullopancreaticobiliary common duct or the ampulloduodenum, and to behave less aggressively than endocrine component-negative carcinoma.     

Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness

OBJECTIVE: The fukutin gene (FKTN) is the causative gene for Fukuyama-type congenital muscular dystrophy, characterized by rather homogeneous clinical features of severe muscle wasting and hypotonia from early infancy with mental retardation. In contrast with the severe dystrophic involvement of skeletal muscle, cardiac insufficiency is quite rare. Fukuyama-type congenital muscular dystrophy is one of the disorders associated with glycosylation defects of alpha-dystroglycan, an indispensable molecule for intra-extra cell membrane linkage. METHODS: Protein and functional analyses of alpha-dystroglycan and mutation screening of FKTN and other associated genes were performed. RESULTS: Surprisingly, we identified six patients in four families showing dilated cardiomyopathy with no or minimal limb girdle muscle involvement and normal intelligence, associated with a compound heterozygous FKTN mutation. One patient died by rapid progressive dilated cardiomyopathy at 12 years old, and the other patient received cardiac implantation at 18 years old. Skeletal muscles from the patients showed minimal dystrophic features but have altered glycosylation of alpha-dystroglycan and reduced laminin binding ability. One cardiac muscle that underwent biopsy showed altered glycosylation of alpha-dystroglycan similar to that observed in a Fukuyama-type congenital muscular dystrophy patient. INTERPRETATION: FKTN mutations could cause much wider spectrum of clinical features than previously perceived, including familial dilated cardiomyopathy and mildest limb girdle muscular dystrophy.