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Biomedical subjects

K Isshiki

Publications and source records attributed to K Isshiki.

At least 55 records · Page 3Linked to original sources
PubMed1994

Chromosome 9 deletion in sporadic and familial melanomas in vivo.

Twenty microsatellite loci on chromosome 9 were analysed for allelic losses in DNAs from 30 uncultured melanomas from 25 patients, relative to DNA from autologous peripheral blood lymphocytes. All patients were constitutionally heterozygous at several loci, and loss of heterozygosity (LOH) affecting 9p was observed in melanoma DNAs from 18 individuals (72%). Observations of losses of identical alleles in different metastatic lesions from the same patients, and of LOH in a vertical growth phase primary melanoma, were consistent with previous reports of chromosome 9 deletion early in melanoma development. LOH data suggested the loss of entire copies of chromosome 9 in 11 cases, and the terminal deletion of all or a portion of 9p in six cases. A somatic interstitial deletion of 9p between D9S162 and D9S169 was seen in a familial melanoma. This 21 cM deleted region corresponded with the previously reported positions of homozygous deletions in melanoma cell lines, and of the familial melanoma susceptibility locus (MLM). As 16 of the 18 cases of 9p LOH in the present study were observed in individuals with no family history of melanoma, it is likely that the MLM locus plays a role in the development of most sporadic melanomas.

Chromosome Deletion↗
PubMed1993

Chromosome 10 allelic loss in malignant melanoma.

The involvement of tumor suppressor genes in the progression of melanoma has been suggested by the frequent deletion of specific regions of the genome in melanoma. In this study, a panel of 18 surgically removed melanomas from 15 patients was analyzed for loss of heterozygosity (LOH) at 10 polymorphic loci on chromosome 10. LOH was observed in 7 (50%) of 14 informative patients. LOH data suggested that melanomas from 5 patients had lost entire copies of chromosome 10, and that melanomas from 2 patients had lost copies of 10q. In contrast, LOH was not observed on chromosome 15, 20, or 21. These results are consistent with previous cytogenetic observations and provide indirect evidence that there is a tumor suppressor gene on the long arm of chromosome 10 which is relevant to melanoma development.

Alleles↗
PubMed1993

P-glycoprotein expression in hepatocellular carcinoma.

In hepatocellular carcinoma cell lines, the intensity of staining with the monoclonal antibody C-219 to the multidrug-resistant gene (mdr1) product P-glycoprotein and the intensity of the band at a molecular weight of 170 KDa on Western blot were associated closely with resistance to Adriamycin but not with the resistance to cis-dichlorodiamine platinum (CDDP). In clinical specimens, noncancerous liver tissue was regularly stained with this antibody on the biliary canalicular front of the hepatocyte cell membrane. In liver cancer tissue, however, regular staining as in the noncancerous regions of the liver was observed in only 16% of the patients, irregular staining was seen in only 24%, and no staining was seen at all in 60%. Staining of P-glycoprotein with the C-219 antibody is technically simple and is useful for studying the role of P-glycoprotein in drug-resistant hepatocellular carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Hemangiopericytomatous meningioma metastasized to the liver: report of a case and review of the literature.

A 54-year-old male was admitted to our hospital for treatment of a liver tumor which was pointed out by screening ultrasonography. Computed tomography revealed a tumor in the right lobe of the liver measuring 7 cm in diameter. Angiography revealed a hypervascular tumor. A hepatocellular carcinoma or hypervascular metastatic tumor was suspected. A right hepatic lobectomy was performed. The patient had previously undergone operations for a hemangiopericytomatous meningioma in the occipital fossa in 1972 and 1977. The histological findings of the liver tumor were identical to those for hemangiopericytomatous meningioma, so the etiology was considered to be liver metastasis from the previous meningioma. Nineteen cases of extracranial metastasis of hemangiopericytomatous meningioma have been reported in the literature, but hepatic resections of this metastasizing tumor have been very rare.

Brain Neoplasms↗
PubMed1992

Application of the chemiluminescent assay to cytotoxicity test: detection of menadione-catalyzed H2O2 production by viable cells.

Menadione-catalyzed H2O2 production by viable cells is proportional to viable cell number. The correlations between the viable cell number and the concentration of H2O2 produced are determined with the rapid chemiluminescent assay (S. Yamashoji, T. Ikeda, and K. Yamashoji, 1989, Anal. Biochem. 181, 149-152). This chemiluminescent assay of viable cells requires only 10 min and is much faster than NR (neutral red) inclusion and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction assays, which require 3-5 h. When viable cells are incubated with antitumor drugs, detergents, mycotoxins, and glycoalkaloids for 24-48 h, a decrease in menadione-catalyzed H2O2 production in a dose- or incubation time-dependent manner is observed. In general, the 50% inhibition concentration determined by the chemiluminescent assay is lower than that determined by NR inclusion and MTT reduction assays, and the order of relative cytotoxic effects of agents is the same among these assays. Furthermore, clear cytotoxic effects are observed by the chemiluminescent assay after 1 h exposure of trypsinized cells to toxic compounds. Therefore, the chemiluminescent assay is expected to be more useful for the rapid detection of cytotoxic compounds than NR inclusion and MTT reduction assays.

3T3 Cells↗
PubMed1991

The potential role of postoperative hepatic artery chemotherapy in patients with high-risk hepatomas.

The relationship between operative findings of hepatoma and the postoperative prognosis was studied to clarify indications for adjuvant hepatic arterial chemotherapy after hepatectomy. The results of adjuvant hepatic arterial chemotherapy using 0.4 mg/kg of doxorubicin and 0.12 mg/kg of mitomycin C and infusion of 5-fluorouracil were reported. One hundred sixty patients who had undergone hepatectomy for hepatoma were studied. In the operative findings of hepatoma, with a surgical margin of less than 10 mm, intrahepatic metastasis, tumor embolus in the second or more proximal branch of the portal vein, or lack of capsule formation related to the prognosis were the risk factors for recurrence. In 132 patients with these risk factors the survival rate of 19 patients with adjuvant arterial chemotherapy was significantly higher than for the 113 patients without it. Adjuvant hepatic arterial chemotherapy thus may be an effective therapy and should be studied prospectively in patients undergoing hepatectomy for high-risk hepatoma.

Adult↗
PubMed1991

Kinetic analysis of dehydropeptidase-I and comparative in vitro and in vivo stabilities of PS-5 derivatives modified at the C-3 side chain.

With partially purified kidney dehydropeptidase-I (DHP-I) preparations, the hydrolysis kinetics of glycyldehydrophenylalanine (Gly-dPh) by DHP-I were found to be completely non-Michaelian, whereas those of PS-5 and imipenem were composed of at least two-phase reactions which were also observed using Bacillus cereus type II beta-lactamase. Thus the DHP-I stabilities of 34 PS-5 carbapenem derivatives which were synthesized by chemical modification at the C-3 side chain of PS-5 were examined in vitro using fresh mouse, dog and human DHP-I preparations, and are tentatively expressed in reference to the DHP-I stabilities of PS-5. The in vitro DHP-I stability of PS-5 was significantly improved by introduction of basic side chains and cysteines at C-3. More particularly, the D-cysteinyl side chain was more stable relative to DHP-I than the L-cysteinyl. In vivo, however, the degree of improvement of the DHP-I-stability by chemical modification at C-3 was not sufficient enough to establish therapeutically effective levels of serum concentrations and urinary recoveries of the carbapenem derivatives after parenteral administration.

Animals↗
PubMed1991

Clinical evaluation of plasma abnormal prothrombin (des-gamma-carboxy prothrombin) in hepatobiliary malignancies and other diseases.

Des-gamma-carboxy prothrombin (DCP), a protein induced by vitamin K absence or antagonist-II (PIVKA-II) was measured in the plasma of patients with primary hepatocellular carcinoma and those with various other hepatobiliary and pancreatic diseases. DCP levels were determined by enzyme immunoassay (E-1023), using an anti-DCP monoclonal antibody. Forty-two of the 91 patients (46.2%) with hepatocellular carcinoma had abnormally elevated levels of DCP, whereas only one of the 24 patients with hepatic cirrhosis showed a slight increase. An increase was also observed in some patients with obstructive jaundice. There was no correlation between plasma levels of DCP and those of serum alpha-fetoprotein (AFP). In most patients with hepatocellular carcinoma, plasma DCP levels normalized after curative surgical resection. Plasma DCP levels were not related to the plasma concentration of vitamin K in the patients with hepatocellular carcinoma. Plasma DCP determination may be useful in the diagnosis and postoperative monitoring of the response of hepatocellular carcinoma.

Biliary Tract Diseases↗
PubMed1990

Inhibition of epidermal growth factor-induced DNA synthesis by tyrosine kinase inhibitors.

We prepared methyl 2,5-dihydroxycinnamate as a stable analogue of erbstatin, a tyrosine kinase inhibitor. This analogue was about 4 times more stable than erbstatin in calf serum. It inhibited epidermal growth factor receptor-associated tyrosine kinase in vitro with an IC50 of 0.15 micrograms/ml. It also inhibited in situ autophosphorylation of epidermal growth factor receptor in A431 cells. Methyl 2,5-dihydroxycinnamate was shown to delay the S-phase induction by epidermal growth factor in quiescent normal rat kidney cells, without affecting the total amount of DNA synthesis. The effect of erbstatin on S-phase induction was smaller, possibly because of its shorter life time.

Animals↗
PubMed1990

Antibacterial activity and chemical modifications of PS-5 at the C-3 side chain.

Using PS-5 as starting material, the effects of chemical modification at the C-3 side chain were studied on the antibacterial activity against Gram-positive and Gram-negative bacteria including beta-lactamase-producers. Among 35 side chains tested, 4-pyridylthio showed the highest antibacterial activity against the Gram-positive bacteria, and D-cysteinyl against the Gram-negative microbes. In general, compared with acetamidoethylthio in PS-5, basic side chains showed improved antibacterial activity against the staphylococci and pseudomonads, whereas the antibiotic activity against the Gram-negative bacteria decreased with bulky side chains. The introduction of 6-aminopenicillanate and 7-aminocephalosporanate to the C-3 side chain of carbapenem significantly reduced the antibacterial activity against the beta-lactamase-producing microbes.

Gram-Negative Bacteria↗
PubMed1990

Inhibition of tyrosine kinase and epidermal growth factor receptor internalization by lavendustin A methyl ester in cultured A431 cells.

Lavendustin A is a novel microbial secondary metabolite that strongly inhibits tyrosine kinase in vitro. But, since it was found that it did not inhibit tyrosine kinase in situ, possibly because of its poor penetration into the cells, the authors therefore synthesized a methyl ester derivative of lavendustin A. Lavendustin A methyl ester inhibited autophosphorylation and internalization of epidermal growth factor receptor in cultured A431 cells. It also inhibited phosphatidylinositol kinase in vitro and phosphatidylinositol turnover in situ.

Cells, Cultured↗
PubMed1990

[Studies on the effectiveness of adjuvant hepatic arterial chemotherapy after hepatectomy for primary or metastatic liver cancer].

From January 1980 to March 1990, 399 cases of primary liver cancer (hepatocellular carcinoma 357, cholangiocellular carcinoma 42) and 148 cases of metastatic liver cancer were treated in our hospital. Some 222 of H.C.C (hepatocellular carcinoma), 20 of C.C. (cholangiocellular carcinoma) and 42 of metastatic liver cancer were resected; 24 of H.C.C, 2 of C.C and 22 of metastatic cancer received adjuvant hepatic arterial chemotherapy, in which anti-cancer drugs were administered with oily contrast medium Lipiodol in hepatic artery. The relationship between operative findings and postoperative prognosis was studied in 168 resected H.C.C cases and risk factors for recurrence were determined. Risk factors are TW(+), which means that the cancer remains macroscopically within 1 cm of surgical margin; IM(+), which means intrahepatic metastasis exists; more than Vp2, which means tumor embolus exists in the second or more proximal branch of the portal vein; and Fc(-), which means lack of capsule formation. In 132 cases with the risk factors, the survival rate of 19 cases with adjuvant arterial chemotherapy was significantly higher than that of 113 cases without it. In the cases of liver metastasis of colon cancer, resection of metastases and adjuvant hepatic arterial chemotherapy improved the prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Studies on drug release from anti-cancer drug suspended Lipiodol].

In case of an arterial infusion chemoembolization therapy for primary or metastatic liver cancer, gradual release of the anti-cancer drug from lipiodol is a very important factor for a higher drug concentration in the tumor and for longer contact. We studied basic points about what kind of drug form has a gradual drug release. We prepared 3 forms of drugs. (1) Powder form: Powder of ADM, MMC and CDDP was suspended in lipiodol with ultrasonic suspender. (2) URO form: ADM and MMC were dissolved with Urografin and mixed with lipiodol. (3) Surfactant form: ADM and MMC were dissolved with water and then mixed with lipiodol using surfactant. We put lipiodol suspension into physiological saline and then stirred water at 100 rpm with the paddle method, measuring drug release from the suspension or emulsion. Powder form had a lowest drug release. In clinical trials, we administered intra-arterially (1) ADM, MMC dissolved with physiological saline water as usually used (physiological saline water form) (2) Powder form; (3) URO from; (1) CDDP solution as usually used was administered; (2) Powder form. Then we studied the changes of serum concentration of ADM, MMC and CDDP. The results indicated that powder form had the lowest drug release. Thus, the water-soluble anti-cancer drugs ADM, MMC and CDDP should be used in powder form.

Antineoplastic Agents↗