Biomedical subjects

H Fujii

Publications and source records attributed to H Fujii.

1,391 records · Page 78Linked to original sources

PubMedDate not supplied

Optimal locoregional immunochemotherapy after tumor-mass reduction for advanced hepatocellular carcinoma.

BACKGROUND/AIMS: This paper will give a description of our attempts to optimize the locoregional immunochemotherapy for advanced hepatocellular carcinoma. MATERIALS AND METHODS: A locoregional immunochemotherapy consisting of continuous recombinant interleukin 2 infusion and intermittent low dose doxorubicin injection was administered to a series of patients. RESULTS: Seventeen Stage IV HCC patients followed the protocol; 11 received IL-2 infusion for more than 6 months, while 6 patients were suspended within 6 months because of new lesions or side effects from IL-2. After suspending IL-2 infusion patients continued to receive ADR injections. In the former group, excellent direct effect on liver tumors accompanied by increase in peripheral NK activity was observed. During periods of higher NK and LAK activity, direct effects on liver tumors were observed as complete remission (CR) in 4 patients and partial remission (PR) in 2 patients. However, long-term observation of NK activity revealed intractable decrease after the 6th to 8th month despite an increase in IL-2 dose. CONCLUSIONS: We have shown the clinical usefulness of our locoregional immunochemotherapy after tumor-mass reduction in extending survival periods for advanced HCC patients. However, clinical effects of IL-2 immunotherapy were not observed in all patients. Further clinical and experimental studies are required to obtain longer-lasting enhancement of NK and LAK activity so that patient survival can be improved.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

A somatic mutation of the p21(Waf1/Cip1) gene in a human adrenocortical adenoma.

The p21(Waf1/Cip1) protein, an inhibitory protein of cellular growth and DNA replication, is induced by the p53 tumour suppressor protein. Any mutations or deletions inactivating the protein may result in unregulated cellular growth. In one aldosterone secreting adrenocortical adenoma, we found a heterozygous deletion of a 111-base-pair (bp) fragment of the p21 cDNA. This deletion resulted in a truncated p21 protein lacking 37 amino acids from codon 65 to 101. The deletion was a somatic mutation, because it was not detected in the DNA of cultured fibroblasts obtained from the same patient. The results suggest that an alteration of the p21 protein may be relevant in inducing an adrenocortical adenoma, a well differentiated and slowly growing benign tumour.

Adenoma↗

PubMedDate not supplied

Current problems with intrahepatic bile duct stones in Japan--congenital biliary malformations as a cause.

BACKGROUND/AIMS: In patients with primary intrahepatic bile duct stones, strictures of the biliary duct are often present, but the relationship between these strictures and the formation of the stones remains controversial. Intrahepatic bile duct carcinoma in association with intrahepatic bile duct stones has recently been reported. The present study attempted to ascertain whether bile stasis induced by congenital biliary strictures is the basis for the formation of stones and occurrence of carcinoma. MATERIALS AND METHODS: We analyzed the location of strictures in 58 patients with strictures in the upper portion of the biliary tract including 38 patients with intrahepatic bile duct stones and 9 with intrahepatic bile duct carcinoma. The cell cycle of epithelial cells from the intrahepatic bile duct were analyzed with using proliferating cell nuclear antigen, which is a immunohistochemical staining method. RESULTS: Fifty six of 58 patients had congenital cystic dilatation of the common bile duct (two infant type and 54 adult type). Thirty eight patients had intrahepatic bile duct stones proximal to the strictures at the hepatic hilum. The location of the strictures were classified into four types. Nine patients had intrahepatic bile duct carcinoma and eight of the 9 carcinomas coexisted with intrahepatic bile duct stones. In the nine patients with intrahepatic bile duct carcinoma, the expression of proliferating cellular nuclear antigen (PCNA) in the carcinoma and the normal bile duct epithelium adjacent to the carcinoma was higher than that of patients with hepatocellular carcinoma without anomaly of the biliary duct. CONCLUSION: Considering the location of the strictures and clinical features, the strictures may have been formed congenitally. Furthermore, adult type cysts of the common bile duct with strictures in the upper portion of the biliary tract are thought to be the basis for the formation of primary intrahepatic bile duct stones. The most appropriate treatment for intrahepatic bile duct stones is thus suggested to be removal of the affected hepatic segment including the region of strictures, combined eventually with hepaticoenterostomy.

Adult↗

PubMedDate not supplied

Anti-invasive activity of synthetic serine protease inhibitors and its combined effect with a matrix metalloproteinase inhibitor.

Tumor invasion into the extracellular matrix (ECM) and basement membrane (BM) is a crucial step of tumor metastasis. In order to investigate the possible therapeutic procedure for the tumor invasion, we investigated the anti-invasive activities of several synthetic serine protease inhibitors. FOY-305, a serine protease inhibitor, showed no cytotoxic activity against human HT-1080 fibrosarcoma cells at concentrations ranging from 0.1 to 100 micrograms/ml, while its analogs ONO-3403 and FO-349 showed slight cytotoxic activities at the concentration of 100 micrograms/ml. These compounds inhibited the activity of urokinase-type plasminogen activator (u-PA) which is one of serine proteases and considered to be associated with tumor invasion and metastasis in fibrin zymography. FOY-305 more potently inhibited the invasion of HT-1080 cells into the reconstituted BM Matrigel, as well inhibited u-PA activity, compared with ONO-3403 and FO-349. These results suggest that the anti-invasive activity of these compounds is consistent with their anti-fibrinolytic activities. In addition, the combined treatment of FOY-305 with FC-336 processing anti-invasive and anti-MMP properties resulted in marked enhancement of anti-invasive activity. In conclusion, FOY-305 inhibited the invasion of tumor cells through interference with the u-PA activity of tumor cells, and this inhibitory activity was augmented by the combination with a MMP inhibitor.

Allylglycine↗

PubMedDate not supplied

99mTc-MIBI scintigraphy as an indicator of the chemosensitivity of anthracyclines in patients with breast cancer.

BACKGROUND: Chemoresistance of tumor cells is involved with many factors, one of which is the P-glycoprotein function to pump anthracyclines out of cells. 99mTc-MIBI accumulates in several tumors, and some of these cells wash out 99mTc-MIBI through P-glycoprotein. MATERIALS AND METHODS: We investigated if the wash-out of 99mTc-MIBI from the tumor in fifteen female patients with breast cancer could be related with the chemosensitivity of anticancer agents; doxorubicin (DOX), epirubicin (FAM), pinorubicin (PINO), mitomycin (MMC), cisplatin (CDDP), and 5-fluorouracil (5-FU), in each tumor tissues. The wash-out of 99mTc-MIBI, defined as retention index, was quantified from an early and delayed 99mTc-MIBI imaging. The chemosensitivity of the anticancer agent, and inhibition ratio, was determined in vitro assay by using surgical specimens obtained from patients who underwent 99mTc-MIBI imaging. P-glycoprotein in the surgical specimen was studied by immunohistochemical staining on its paraffin section using a monoclonal antibody. RESULTS: Inhibition ratio of anthracycline agent, DOX, FAM or PINO, was well correlated with retention index of 99mTc-MIBI with coefficient of 0.75, 0.60, or 0.62, respectively, whereas a poor relationship was observed for MMC and CDDP. The retention indices of 99mTc-MIBI were remarkably small for patients in the P-glycoprotein positive group. CONCLUSION: 99mTc-MIBI retention index quantified from its early and delayed scintigraphy is a good indicator to predict the chemosensitivity of anthracyclines in untreated breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗