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Biomedical subjects

T Teramoto

Publications and source records attributed to T Teramoto.

At least 19 recordsLinked to original sources

Inhibitory effect of anti-epidermal growth factor receptor antibody on a human gastric cancer.

BACKGROUND: Blockading the putative epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha)/EGF receptor autocrine pathway with anti-EGF receptor monoclonal antibody (MoAb) might prevent the growth of tumor. METHODS: The present study was designed to examine the effect of MoAb 528 on the growth of an EGF receptor which was hyperproducing human gastric cancer cells in vitro and in vivo. RESULTS: Treatment with MoAb 528 inhibited the growth of cultured cells in a dose-dependent manner. Twenty micrograms of MoAb 528 given intraperitoneally after inoculation of 1 x 10(6) cells and 200 micrograms of the MoAb 528 given after inoculation of 1 x 10(7) cells to athymic mice inhibited the growth of the xenograft. Twenty micrograms of MoAb 528 from a miniosmotic pump, which releases its contents over 2 weeks, also prevented the growth of the xenograft when the treatment was started on the day after tumor inoculation. However, no inhibitory effect was observed when the treatment was started 3 weeks after inoculation. The binding capacity of 125I-EGF on the MoAb treated tumors was diminished in comparison with control tumors. CONCLUSIONS: The results suggest that MoAb 528 blocks the EGF or TGF-alpha/EGF receptor signal pathway, resulting in the inhibition of cancer cell growth. This MoAb 528 may therefore be an effective antitumor agent against human gastric cancer that shows expression of the EGF receptor.

Animals

Morphological analysis of the cervical spinal canal, dural tube and spinal cord in normal individuals using CT myelography.

To verify the conventional concept of "developmental stenosis of the cervical spinal canal", we performed a morphological analysis of the relations of the cervical spinal canal, dural tube and spinal cord in normal individuals. The sagittal diameter, area and circularity of the three structures, and the dispersion of each parameter, were examined on axial sections of CT myelograms of 36 normal subjects. The spinal canal was narrowest at C4, followed by C5, while the spinal cord was largest at C4/5. The area and circularity of the cervical spinal cord were not significantly correlated with any parameter of the spinal canal nor with the sagittal diameter and area of the dural tube at any level examined, and the spinal cord showed less individual variation than the bony canal. Compression of the spinal cord might be expected whenever the sagittal diameter of the spinal canal is below the lower limit of normal, that is about 12 mm on plain radiographs. Thus, we concluded that the concept of "developmental stenosis of the cervical spinal canal" was reasonable and acceptable.

Adolescent

CETP is a determinant of serum LDL-cholesterol but not HDL-cholesterol in healthy Japanese.

Cholesteryl ester transfer protein (CETP) is one of the factors that regulate plasma levels of HDL-cholesterol. To identify the factors that may regulate CETP activity, and to determine to what extent CETP is correlated with physiologic concentrations of lipoprotein, we performed an epidemiologic study in 586 healthy volunteers (317 males and 269 females mean age 52.2 +/- 10.9 years). CETP activity in these subjects was 192.96 +/- 48.73 (mean +/- S.D.) nmol/ml/h and distributed to a wide range (60-450 nmol/ml/h). Using multiple regression analysis, we found significant positive correlations between CETP activity and LDL-cholesterol (P < 0.03), apolipoprotein (apo) E (P < 0.005) and LCAT activity (P < 0.001). CETP activities showed significant negative correlation with apo A-I (P < 0.03). However, CETP activity showed no significant correlation either with HDL cholesterol or with apo B. One-way layout analysis of variance showed that alcohol drinking and cigarette smoking significantly reduced CETP activity, but there was no significant association between CETP activity and body mass index. Although CETP activities were significantly higher in females than in males (P < 0.001), multiple regression analysis showed no correlation between CETP activity and age in either the males or the females. Our results suggest that CETP activity regulates the concentration of apo A-I and LDL-cholesterol, and that such activity may be influenced by gender, alcohol consumption and cigarette smoking.

Adult

Dose-dependent effect of niceritrol on plasma lipoprotein-a.

Lipoprotein-a, Lp(a), is a variant form of low density lipoprotein (LDL) that contains apolipoprotein-a, whose structure has 75-85% homology with plasminogen. Elevated plasma levels of Lp(a) are considered to be one of the independent risk factors for cardiovascular disease. We studied the effects of niceritrol, a nicotinic acid derivative, on plasma Lp(a) levels in 72 patients with hypercholesterolaemia. The dose of niceritrol was increased every 4 weeks, from 750 to 1500 and then to 2250 mg day-1. The final dose was adjusted to obtain a plasma cholesterol level less than 5.69 mmol l-1. Niceritrol led to significant decreases in plasma levels of median Lp(a), from 16.1 mg dl-1 (interquartile intervals, 8.7 to 32.8) to 11.1 mg dl-1 (interquartile intervals, 6.6 to 21), the mean reduction rate being 17.6%. In the group with pretreatment Lp(a) levels of over 20 mg dl-1, Lp(a) decreased by 10.0, 22.0 and 31.8% at the doses of 750, 1500, and 2250 mg day-1, respectively. In the group with levels less than 20 mg dl-1, only the dose of 2250 mg day-1 was effective in the reduction of Lp(a). The results suggest that the reduction of Lp(a) was dependent on the dose of niceritrol and on the pretreatment level of Lp(a). In conclusion, niceritrol is effective, in a dose-dependent manner, for reducing Lp(a) levels.

Aged

[Optimal dosage of UFT + MMC combination chemotherapy for advanced colorectal cancer--phase I/II study of combination chemotherapy of MMC with 2-week intervals and intermittent UFT administration--Study Group of UFTM Therapy for Advanced Colorectal Cancer].

A combined phase I/II study (UFTM) of tegafururacil (UFT) and mitomycin C (MMC) was performed to find the optimal dosage for advanced colorectal cancer. The study consisted of two parts. The first part confirmed the safety of UFTM and determined the administered doses. The second part evaluated the clinical response of UFTM. Based on the first part, the dosage regimen in the second part was established as follows; the treatment course consisted of 4 weeks and a bolus dose of MMC 6 mg/m2 was given every 2 weeks with daily oral UFT 400 mg/m2 for 5 consecutive days followed by 2 drug-free days; MMC was not given in the third course, and the treatment cycle of the above-mentioned 3 courses was repeated thereafter. In the second part, 26 of 28 patients could be evaluated for toxicity. Grade 3 or 4 toxicities were: anorexia 2, nausea and vomiting 1, leukopenia 1, and 2 cases of thrombocytopenia. The clinical responses of UFTM showed 1 CR and 4 PR in the 21 patients who could be evaluated for response (23.8%). The response rate was 38.5% (5/13) in patients naive to chemotherapy. UFTM can be performed effectively at outpatient clinics as long-term chemotherapy.

Adolescent

Abnormal B cell response of protein kinase C in some common variable immunodeficiency.

The localization of protein kinase C (PKC) was investigated in B cells or B cell lines derived from patients with common variable immunodeficiency (CVI) and healthy controls. Stimulation of the healthy control B cells by phorbol ester or anti-mu induced PKC activation and translocation to the plasma membrane after 10 min. In contrast, in the CVI-B cells, no apparent PKC translocation was induced by either phorbol ester or anti-mu stimulation. These results suggest that the pathogenesis in some CVI patients might involve defects in the pathway of PKC activation.

Adult

[Role of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery].

Examinations of peritoneal lavage smears (LC) and gastric wall brushing smear cytology (BC) appear to be important for determining accurately the stage of gastric cancer. We have been carrying out such examinations during gastric cancer surgery for 7 years. In the present study, we evaluated the results obtained from 287 patients with gastric cancer. Tumor invasion and peritoneal dissemination were correlated with a positive incidence of cancer cells in LC and/or BC. Gastric cancer showing serosal invasion was classified into positive for LC and/or BC and negative for LC and/or BC. Patients positive for LC and/or BC had a poorer prognosis. For future gastric cancer treatment, patients positive for peritoneal cytology are expected to be targeted for intensive treatment during or before surgery.

Adenocarcinoma

Liver colonization competence governs colon cancer metastasis.

Tumors that metastasize do so to preferred target organs. To explain this apparent specificity, Paget, > 100 years ago, formulated his seed and soil hypothesis; i.e., the cells from a given tumor would "seed'' only favorable "soil'' offered by certain groups. The hypothesis implies that cancer cells must find a suitable "soil'' in a target organ--i.e., one that supports colonization--for metastasis to occur. We demonstrate in this report that ability of human colon cancer cells to colonize liver tissue governs whether a particular colon cancer is metastatic. In the model used in this study, human colon tumors are transplanted into the nude mouse colon as intact tissue blocks by surgical orthotopic implantation. These implanted tumors closely simulate the metastatic behavior of the original human patient tumor and are clearly metastatic or nonmetastatic to the liver. Both classes of tumors were equally invasive locally into tissues and blood vessels. However, the cells from each class of tumor behave very differently when directly injected into nude mouse livers. Only cells from metastasizing tumors are competent to colonize after direct intrahepatic injection. Also, tissue blocks from metastatic tumors af fixed directly to the liver resulted in colonization, whereas no colonization resulted from nonmetastatic tumor tissue blocks even though some growth occurred within the tissue block itself. Thus, local invasion (injection) and even adhesion to the metastatic target organ (blocks) are not sufficient for metastasis. The results suggest that the ability to colonize the liver is the governing step in the metastasis of human colon cancer.

Adenocarcinoma

Binding of vitamin D to low-density-lipoprotein (LDL) and LDL receptor-mediated pathway into cells.

The present study was undertaken to identify serum components other than vitamin D-binding proteins that bind to 1,25(OH)2 D3, and its analog. The binding rate of 1,25(OH)2 D3, 22-oxa-1,25(OH)2D3 (OCT) or 25(OH) D3 to total lipoprotein(TLP) represented 16.7%, 4.65%, and 3.11% of total counts added, respectively. Polyacrylamide gel electrophoresis of the TLP revealed that 1,25(OH)2 D3 and OCT were associated with LDL. The binding studies of OCT-bound LDL to the fibroblasts showed specific pathway to the cells mediated by LDL-receptor. These findings may have important implications in understanding the mechanisms of the diverse biological actions of 1,25(OH)2 D3 and in designing a novel delivery system for vitamin D analogs.

Apolipoprotein B-100

Two types of calcium channels sensitive to omega-agatoxin- TK in cultured rat hippocampal neurones.

We characterized the electrophysiological properties of calcium channels in cultured rat hippocampal neurones using omega-agatoxin-TK (omega-Aga-TK) and compared them with those of the P-type channel and the BI (alpha 1A) channel which resembles the Q-type channel. Two types of omega-Aga-TK-sensitive calcium channels were detected in hippocampal neurones. The first type showed slow inactivation, high sensitivity to omega-Aga-TK and low reversibility from omega-Aga-TK-induced block, resembling the P-type channel. The second type showed fast inactivation, low sensitivity to omega-Aga-TK and high reversibility from omega-Aga-TK-induced block. These results suggest that the second type of calcium channel (Q-type-like) plays a prominent role in the hippocampal synaptic transmission.

Agatoxins

Isolation and characterization of a peptide isomerase from funnel web spider venom.

A novel peptide isomerase was purified from the venom of funnel web spider, Agelenopsis aperta. The complete primary structure of the isomerase has been established by sequence analyses of polypeptide chains, assignments of disulfide bridges, carbohydrate analyses, and mass spectrometry of sugar chains. The isomerase was found to be a 29-kDa polypeptide that consists of an 18-residue light chain and a 243-residue heavy chain connected by a single disulfide bridge. The heavy chain contains three intramolecular disulfide bridges and one N-linked oligosaccharide chain with a simple trimannosyl core structure. A sequence homology search showed a significant similarity of the enzyme with serine proteases, particularly around a putative catalytic triad of the isomerase. The isomerase specifically interconverts the configuration of Ser46 of a 48-amino-acid peptide, omega-agatoxin-TK, and the conversion rate from L-Ser to D-Ser was approximately two times faster than the reverse reaction.

Amino Acid Isomerases

Clinical efficacy of fluvastatin for hyperlipidemia in Japanese patients.

The objective of the study was to evaluate the efficacy and safety of fluvastatin in patients with hypercholesterolemia, including heterozygous familial hypercholesterolemia, in a 1-year study (a 12-week open assessment, followed by 40 weeks of active treatment). Of the 337 patients enrolled in the study, the effects of fluvastatin were analyzed in 296 patients at baseline and at 12 weeks. Of these, 265 were receiving 20 mg/day fluvastatin at week 12 and in 20 patients the dose had been increased to 30 mg/day; 11 patients violated the dosing protocol. A total of 229 patients continued into the 40-week, long-term phase, and 212 patients were analyzed at baseline and after 24 and 52 weeks. At the end of treatment, 153 evaluable patients were still taking 20 mg/day fluvastatin, 1 was taking 10 mg/day, and 48 patients were taking 30 mg/day, and 10 were taking 40 mg/day. In the 20 mg/day fluvastatin group, low density lipoprotein cholesterol (LDL-C) levels decreased by 24.1% at week 12 and by 29.3% at week 52. In those patients requiring the higher doses, the corresponding reductions in LDL-C were 20.2% (week 12) and 26.7% (week 52). Total cholesterol was also reduced at week 12 by 17.0% (20 mg/day) and 15.7% (20-30 mg/day), and at week 52 by 20.4% (< or = 20 mg/day) and 19.2% (> or = 30 mg/day). Throughout the study, fluvastatin was generally well tolerated and no serious clinical adverse events were observed. In conclusion, long-term treatment of hypercholesterolemia with fluvastatin at dosages of 20-40 mg daily can be considered both safe and effective.

Anticholesteremic Agents

Alteration of expression in integrin beta 1-subunit correlates with invasion and metastasis in colorectal cancer.

We have investigated the expression of the integrin beta 1 subunit in 51 colorectal cancer tissues using immunoblotting and have determined the relationship between expression and clinical stage. In comparison with normal mucosa the pre-beta-subunit (the precursor of beta 1-subunit) was increased in 15 cases and decreased in two cases, and expression of the beta 1-subunit was decreased in two cases. These alterations of expression of the beta 1-subunit were significantly correlated with lymph node metastasis and depth of invasion (P < 0.01). These results suggest that integrin plays an important role in the invasion and metastasis of colorectal cancer.

Colorectal Neoplasms

Expression of sialyl Lewis(a) as a new prognostic factor for patients with advanced colorectal carcinoma.

BACKGROUND: Sialyl Lewis(a) antigen (SLA) is considered to be a cancer-associated carbohydrate antigen. METHODS: A total of 309 surgically resected primary colorectal cancer specimens and 501 associated metastases to regional lymph nodes were analyzed immunohistochemically using a monoclonal antibody (NS19-9) recognizing SLA. The specimens were obtained from 1981 to 1988 at the Department of Surgery, Keio University School of Medicine (Tokyo, Japan). RESULTS: Sialyl Lewis(a) antigen expression was detected in 75.4% (233/309) of the primary tumors and in 78.5% (99/126) of the metastases to regional lymph nodes. Significantly stronger expression was noted in the regional lymph node metastases than in the primary lesions (P = 4.5E-7). Sialyl Lewis(a) antigen expression in the primary tumors correlated significantly with regional lymph node metastasis (P < 0.005), recurrence (P < 0.005), and postoperative survival (P < 0.001) as determined by univariate analysis. Sialyl Lewis(a) antigen expression in the regional lymph node metastases also correlated strongly with recurrence (P < 0.005) and survival (P < 0.01). As determined by multivariate analysis, SLA expression in the primary tumor correlated strongly with recurrence (P = 3.0E-6) and survival (P = 6.9E-3). CONCLUSIONS: Sialyl Lewis(a) antigen expression in primary tumors and metastases to regional lymph nodes is a useful marker for evaluating tumor aggressiveness and prognosis in patients with advanced colorectal cancer.

Aged

K-ras gene mutations in early colorectal cancer ... flat elevated vs polyp-forming cancer....

K-ras gene mutations in early colorectal cancer were detected by two-step sensitive polymerase chain reaction (PCR) and enzyme digestion method. Early colorectal cancer was classified into flat elevated cancer or polyp-forming cancer according to morphology and presence of adenomatous components. A total of 60 paraffin-embedded tissue specimens from patients with early colorectal cancer were analysed. K-ras codon 12 mutations were detected in 23.3% (7/30) of flat elevated cancer and 63.3% (19/30) of polyp-forming cancer. The incidence of K-ras codon 12 mutations in flat elevated cancer was significantly lower than in polyp-forming cancer (P < 0.01). These data suggested that K-ras gene mutations may be correlated with morphology or clinical features in flat elevated cancer, and that flat elevated cancer may originate from a pathway different from adenoma-carcinoma sequence.

Base Sequence

Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer.

The EGF stimulation system for growth regulation is implicated in normal and neoplastic cell proliferation. The role of EGF, the EGF receptor, and c-erbB-2 in human gastric cancer is reviewed on the basis of several reports, which have been mainly oriented toward their clinical significance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric cancer is correlated with the degree of gastric wall invasion and lymph node metastasis. The 5-year survival of patients with EGF-positive tumors is worse than that of patients with EGF-negative tumors. The presence of EGF in human gastric cancer may therefore represent a higher malignant potential. Fifteen percent of gastric cancers (n = 352) were also shown to be positive for both EGF and the EGF receptor immunohistochemically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibiting EGF and the EGF receptor simultaneously show a greater degree of local invasion and lymph node metastasis. Increased expression of EGF receptor protein in gastric cancer appears to be related to biologic aggressiveness, although gene amplification has occurred only to a small extent. Twelve percent of gastric cancers (n = 486) were found to be positive for c-erbB-2. This type of tumor has a frequent metastasis, and patients with c-erbB-2-positive cancer have a poorer prognosis than those with c-erbB-2-negative tumors. Selective blockade of the EGF receptor and c-erbB-2 from their ligands with monoclonal antibodies (MoAbs) inhibits the growth of human gastric cancer xenografts. These MoAbs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c-erbB-2.

Epidermal Growth Factor