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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 1,549 records · Page 86Linked to original sources
PubMedDate not supplied

Hepatocyte growth factor and c-Met/hepatocyte growth factor receptor in pulmonary adenocarcinomas: an evaluation of their expression as prognostic markers.

The expression of hepatocyte growth factor (HGF) and its receptor, c-Met, was investigated immunohistologically in tissue specimens of patients with a pulmonary adenocarcinoma. The prognosis was significantly worse in the HGF-positive or c-Met-positive patients than in the negative patients. Multivariate analysis showed that c-Met had a significant effect on the prognosis, whereas HGF did not. Our findings suggest that HGF and c-Met play an important role in tumor progression and that c-Met can be a useful prognostic marker for pulmonary adenocarcinomas.

Adenocarcinoma↗
PubMedDate not supplied

Transforming growth factor-beta isoforms expressions in pulmonary adenocarcinomas as prognostic markers: an immunohistological study of one hundred and twenty patients.

The transforming growth factor (TGF)-beta1, TGF-beta2 and TGF-beta3 expressions were immunohistologically studied in tissues specimens from 120 patients with a pulmonary adenocarcinoma. The results of a univariate analysis indicated that the expression of each of the TGF-beta isoforms correlated with the prognosis. Of the three prognostic factors examined using Cox's stepwise regression model, the TGF-beta1 isoform was found to correlate with survival. These findings suggest that TGF-beta isoforms play an important role in tumor progression and that the TGF-beta1 isoform is a useful prognostic marker for pulmonary adenocarcinomas.

Adenocarcinoma↗
PubMedDate not supplied

Suramin inhibits the growth of non-small-cell lung cancer cells that express the epidermal growth factor receptor.

The epidermal growth factor (EGF) is a potent growth factor that is believed to enhance the proliferation of cancer cells by a paracrine or autocrine mechanism. EGF transduces various signals and finally stimulates cell proliferation upon binding to cell surface receptors. Prevention of the association of this peptide with its receptors might lead to the development of new modalities for treatment of lung cancer. Several investigators have reported that suramin has antiproliferative activity against cancer cells that express EGF receptors (EGF-R), and that it acts by blocking the binding of the ligand to its receptor. In this study, we analyzed the antitumor effect of suramin using two lines of lung cancer cells (A549 and PC-13), which express EGF-R, and a variety of assays. Receptor-binding assays confirmed that A549 and PC-13 cells have cell surface receptors for EGF. Suramin inhibited the binding of EGF to these receptors. EGF and fetal bovine serum (FBS) stimulated the proliferation of cells, but suramin inhibited these effects in a dose-dependent fashion. Suramin at 200 microg/ml reduced the growth of A549 and PC-13 cells by 25 and 15%, respectively, in medium that contained 1% FBS. Paradoxically, the concentrations of suramin that inhibited cell proliferation were lower than those that were effective in inhibiting the binding of EGF to its receptor. Although expression of c-fos and c-myc mRNA increased when cells were stimulated by EGF or FBS, suramin at 200 microg/ml did not markedly alter such expression. Suramin partially blocked the EGF-induced progression of the cell cycle from the G0/G1 to the S phase. These results suggest that suramin partially blocks EGF signal transduction. Suramin probably inhibits cell proliferation by inhibiting intranuclear enzymes, as well as by partial blockage of EGF signal transduction.

Anticarcinogenic Agents↗
PubMedDate not supplied

Detection of the circulating lung cancer marker LCAP with a new monoclonal antibody TRD-L1.

Lung Cancer Associated Protein (LCAP) is a high molecular weight glycoprotein defined by the monoclonal antibody (MAb) DF-L1 prepared against a primary adenocarcinoma of the lung. Previous studies have demonstrated that LCAP circulates at elevated levels in patients with lung cancer. However, a suitable assay for monitoring LCAP levels has not been available. The present work describes the development of a double-determinant LCAP assay using MAb TRD-L1 as the capture antibody and MAb DF-L1 as the tracer. In 60 normal subjects, the mean LCAP level was 4.8 U/ml with 2 (3.3%) subjects having values > 12 U/ml (mean + 2SDS). By contrast, 37 of 67 (55.2%) patients with lung cancer had LCAP levels > 12 U/ml. Moreover, only 14 of 203 (6.9%) patients with benign lung disease had elevated levels. LCAP levels were most commonly elevated (62.7%) in patients with adenocarcinoma of the lung and with advanced disease. These results indicate that LCAP as detected by MAb TRD-L1 is a potentially useful marker for the evaluation of patients with lung cancer.

Adenocarcinoma↗
PubMedDate not supplied

Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression.

To determine whether cancer patients with tumor suppressor gene abnormality survive for a shorter time when their growth was stimulated by growth factors, we examined 290 non-small cell lung cancer (NSCLC) specimens for p53 and epidermal growth factor receptor (EGFR) protein expressions using immunohistochemical staining. The distribution of cases by pathological stage of tumor was 155 cases of stage I, 30 cases of stage II, 96 cases of stage III and 9 cases of stage IV. Pathological types were 142 adenocarcinomas, 127 squamous cell carcinomas, 17 large cell carcinomas and 4 other types of malignancy. Immunohistochemical staining was performed on the formalin fixed, paraffin-embedded materials with monoclonal antibodies DO-7 and clone EGFR.133. positive staining for EGFR was seen in 124 (42.8%) cases. More EGFR positive cases were found in squamous cell carcinomas than in non-squamous cell carcinomas (p=0.0121). Staining for p53 protein was observed in 147 (50.7%) specimens. Multivariate proportional hazard model analyses revealed EGFR protein expression as a risk factor in the patients with NSCLC (p=0.0240). Patients negative for both EGFR and p53 survived for a longer period of time (p=0.0427).

Adenocarcinoma↗
PubMedDate not supplied

[A case of the cerebellar atrophy and pseudo-hyperchloremia as a clue to diagnose chronic bromvalerylurea intoxication].

A 36-year-old woman was admitted to our hospital because of walking disturbance and dizziness. Her neurological examination showed psychiatric disturbance, truncal and limb ataxia, wide-based gait. She has taken 3 g of bromvalerylurea daily. The laboratory test revealed elevated levels of serum chloride (201 mEq/L) and bromide (105 mg/dl), and decreased (-43 mEq/L) anion gap. Brain MRI revealed atrophy of upper part of the vermis and cerebellar hemisphere, and widening of the primary fissure and dilatation of the forth ventricle. Bromvalerylurea, which is an easily available sedative, should be still noted as a cause of cerebellar ataxia. Increased level of serum chloride was useful information for early diagnosis of chronic bromide intoxication.

Adult↗
PubMedDate not supplied

The utility of diffusion-weighted imaging with navigator-echo technique for the diagnosis of spinal epidermoid cysts.

We report a case of a spinal epidermoid cyst in which diffusion-weighted imaging with a navigator-echo technique was useful for the differential diagnosis from other cystic tumors. Motion artifacts are inherent on diffusion-weighted images of the spinal region; however, the navigator-echo technique compensated for this problem and provided high-quality images. Diffusion-weighted imaging with navigator echoes is considered to be a potentially useful tool in the differential diagnosis of spinal cystic tumors.

Adult↗
PubMedDate not supplied

Immunohistochemical detection of cytokeratin 18 and its neo-epitope in human salivary glands and pleomorphic adenomas.

An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which reacts with the product released by the cleavage of cytokeratin 18 (CK18) by activated caspase, was used to investigate the extent of apoptosis in human salivary glands and pleomorphic adenomas. The distribution of CK18 in the salivary glands and adenomas was also determined and compared with that of the product detected by MAb M30. CK18 was detected in the cytoplasm of serous acinar and ductal cells in normal human salivary glands. In pleomorphic adenomas, CK18 was observed mainly in the tumor cells of duct-like structures, but not in those of myxomatous or chondroid tissues. Positive MAb M30 reaction products were found in the cytoplasm of acinar cells in the restricted lobules of normal salivary glands and in the luminal contents of duct-like structures in pleomorphic adenomas. These results suggest that a mechanism which suppresses apoptosis may be linked to the growth of human pleomorphic adenomas.

Adenoma, Pleomorphic↗
PubMedDate not supplied

Metabolism and penetration through blood-brain barrier of parkinsonism-related compounds. 1,2,3,4-Tetrahydroisoquinoline and 1-methyl-1,2,3,4-tetrahydroisoquinoline.

14C-Labeled 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) were synthesized, and their metabolism and tissue distribution were studied. Both compounds showed similar metabolic patterns. In 24 hr after po administration (50 mg/kg) to rats, 76% of TIQ and 72% of 1MeTIQ were excreted unchanged, and 2.7 and 8.7% were excreted as the 4-hydroxyl derivatives, 4-hydroxy-TIQ and 4-hydroxy-1MeTIQ, respectively. Small amounts of N-methylated metabolites, 2-methyl-TIQ (0.4%) and 2-methyl-1MeTIQ (0.7%) were detected. Isoquinoline (2.5%) also was found as a metabolite of TIQ and 1-methyl-3,4-dihydroisoquinoline (1.0%) was found as a metabolite of 1MeTIQ. The concentration of labeled compounds in the brain was about 4.5-fold higher than the blood concentration at 4 hr after dosing, and over 90% was unchanged TIQ or 1MeTIQ. These data indicated that TIQ and 1MeTIQ easily passed through the blood-brain barrier and were concentrated in the brain. Thus, it appears that TIQ and 1MeTIQ as endogenous or exogenous amines may accumulate in the brain and may be related to the onset of Parkinson's disease.

Animals↗
PubMedDate not supplied

Functional maturation of monocytes/macrophages induced by PSK subfractions.

When mouse resident peritoneal macrophages were cultured with PSK (Krestin), a protein-bound polysaccharide extracted from Coriolus versicolor, they became enlarged and elongated and expressed higher NBT-reducing activity. PSK stimulated the production of differentiation-inducing factor and cytotoxic factor by the mouse macrophage-like cell line J774.1, and iodination (incorporation of radioactive iodine into an acid-insoluble fraction) and interleukin-1-like factor production by human peripheral blood monocytes. Among four different PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) was the most potent. Natural and chemically modified glucans had little or no activity. The data suggest that some unique structure of the highest molecular weight fraction of PSK directly stimulates the monocytes/macrophages.

Animals↗
PubMedDate not supplied

Macrophage stimulation activity of antimicrobial N,N-dimethylaminoethyl paramylon.

Pretreatment with N,N-dimethylaminoethyl (DMAE) paramylon significantly protected mice from infection by various microorganisms. When mouse peritoneal macrophages were cultured with DMAE-paramylon, they showed morphological change (spreading) and elevated NBT-reducing activity. Macrophages prepared from DMAE-paramylon-treated mice had higher NBT-reducing activity than those from control mice. On the other hand, carboxymethyl paramylon and paramylon sulfate, which did not induce appreciable antimicrobial activity, failed to stimulate macrophage functions. The data suggest a significant role of macrophages in antimicrobial activity induction by cationized glucans.

Animals↗
PubMedDate not supplied

Prophylactic anti-tumor effect of Hochu-ekki-to (TJ41) by enhancing natural killer cell activity.

We assessed the anti-tumor activity in vivo of a kampo (Chinese) prescription Hocku-ekki-to (TJ41) in the rat and mouse tumor model. The growth of tumors was clearly inhibited in syngeneic animals given TJ-41 prophylactically. The splenic NK cells of TJ-41-treated WKA rats showed enhanced cytotoxicity against tumors including NK-sensitive YAC-1 targets. TJ-41 did not increase the splenic NK cell population, but it appeared that TJ-41 could potentiate the cytotoxic capability of each NK cell. These data indicate that TJ-41 may be useful for prophylactic immunotherapy of cancer. One of the mechanisms of the potent inhibitory effect by TJ-41 on tumor growth might be explained by its enhancement of NK activity.

Animals↗
PubMedDate not supplied

Immunogenicity and involvement in the host's effector mechanisms of the oncogene--induced transformation--associated cell surface antigens.

The clonal expression of oncogene-induced transformation-associated cell surface antigens (TAAs) of a WFB rat fetus fibroblast was analyzed by developing mAbs to TAAs. We identified four TAAs. Two out of four TAAs seemed to be involved in the cytotoxicity by NK cells. One is an hsp-like molecule. These TAAs may play an important role in the antitumor surveillance mechanism by the host immune system. By clarifying the molecular characteristics, it would be possible to apply the genes encoding these molecules in the immunotherapy of cancer.

Animals↗
PubMedDate not supplied

Stimulation of mouse peritoneal macrophages by lignin-related substances.

Various lignified materials, including pine cone extract and a commercial lignin, stimulated the morphological change (spreading) of mouse peritoneal macrophages, and their functional maturation as judged by increase in NBT-reducing activity. When these materials were treated with NaClO2 to decompose the phenolic structure, their activity was completely eliminated, whereas the activity was rather enhanced when they were treated with H2SO4 to decompose their sugar moiety. Some monomeric phenolic compounds structurally related to lignin components and several antitumor glucan derivatives had little or no macrophage stimulating activity. The results strongly suggest the importance of lignin-structure in macrophage activation.

Animals↗
PubMedDate not supplied

Vitamin D-dependent rickets type II: report of three cases.

In this study the dental findings of three patients with vitamin D-dependent rickets (DDR) type II with alopecia, who were treated with large doses of vitamin D3 derivatives, are described. Dental development that is at or near a normal level can be achieved in controlled patients, permitting routine treatment of carious teeth.

Calcifediol↗