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Biomedical subjects

H Eto

Publications and source records attributed to H Eto.

At least 19 recordsLinked to original sources
PubMed2000

Mapping and regulation of the tumor-associated epitope recognized by monoclonal antibody RS-11.

We have previously described a rat monoclonal antibody, RS-11, which recognizes a tumor-associated antigen common to several species. In the present study, we have cloned and characterized the antigen recognized by RS-11. We screened a phage expression library prepared from HeLa cDNA and identified a clone that reacts with RS-11. DNA sequence analysis revealed that this clone contains sequences of keratin 18 (nucleotides 568-1196). We constructed several glutathione S-transferase fusion proteins and synthetic peptides based on this DNA sequence analysis and examined their reactivity with RS-11 to accurately map the RS-11 epitope. We determined that the epitope resides within a region of seven amino acids on the alpha-helix 2B domain of keratin 18 in which two amino acids (Leu(366) and Lys(370)) are completely conserved among intermediate filaments as well as other keratin members that are immunoreactive with RS-11. These two residues are sequentially discontinuous but spatially adjacent. The RS-11 epitope is constitutively present in human primary cultured hepatocytes; however, its immunoreactivity with RS-11 is up-regulated by malignant transformation or stimulation with either epidermal growth factor or transforming growth factor alpha.

Amino Acid Sequence↗
PubMed2000

CD44s expression in human colon carcinomas influences growth of liver metastases.

CD44 is a family of cell-surface adhesion molecules which exist in several isoforms arising from mRNA alternative. Malignant transformation of colonic mucosa is associated with alterations in CD44 expression, which result in up-regulation of high-molecular-weight CD44 isoforms and down-regulation of CD44s. We have demonstrated that stable transfection of CD44s into colon-carcinoma cell lines reduces their tumorigenicity. To understand the influence of CD44s expression on the metastatic potential of human colon carcinomas, we measured the ability of several different CD44s-transfected colon carcinomas to establish experimental liver metastases following splenic inoculation in mice. We observed that introduction of CD44s into 2 different human colon carcinoma cell lines, HT29 and KM12C6, resulted in reduced growth of liver metastases by as much as 75%. To explore the relationship between hyaluronate adhesion and metastasis, we transfected HT29 cells with cDNA encoding a mutant CD44s that does not bind to hyaluronate. HT29 transfectants expressing this mutant CD44s demonstrate an 84% reduction in growth of liver metastases, despite minimal binding to hyaluronate by the mutant CD44s. In concert, these results indicate that CD44s down-regulation, which occurs with malignant transformation of colonic mucosa, is associated with enhanced growth of experimental liver metastases. Consequently, the functional consequences of CD44s down-regulation in colon carcinomas may be just as significant as the consequences of up-regulation of other CD44 isoforms.

Alternative Splicing↗
PubMed2000

Late onset hyalinosis cutis et mucosae.

Two cases of non-familial, late onset (50 and 62-years-old) hyalinosis cutis et mucosae were studied and compared with classical early onset cases. Late onset cases showed essentially the same histological and ultrastructural features described for early onset cases. The late onset variety should be distinguished from other diseases; they resemble systemic amyloidosis and sometimes the adult form of colloid milium.

Age Factors↗
PubMed2000

alpha,alpha-gem-Difluorination of alpha-(alkylthio)acetophenone derivatives with N-fluoropyridinium salts.

The alpha,alpha-gem-difluorination of 2',4'-difluoro-alpha-(methylthio)acetophenone (1a) with N-fluoropyridinium salts gave 2',4',alpha,alpha-tetrafluoro-alpha-(methylthio)acetophenone (3a). This reaction was accelerated by the addition of zinc chloride, zinc bromide or anhydrous iron(III) chloride, and higher yields than the reaction without additives were obtained. The gem-difluorination reaction using FP-T300 in the presence of zinc bromide was applicable to other alpha-(alkylthio)acetophenone derivatives (1).

Acetophenones↗
PubMed2000

New antifungal 1,2,4-triazoles with difluoro(heteroaryl)methyl moiety.

New 1,2,4-triazoles (1) having a difluoro(heteroaryl)methyl moiety were designed and synthesized via 1-aryl-2,2-difluoro-2-(heteroaryl)ethanones (2), which were prepared by two routes starting from the reaction of ethyl 2,2-difluoro(heteroaryl)acetate with phenyllithiums (Route A) and from the reaction of chlorodifluoro(heteroaryl)methane with benzaldehydes (Route B). The compounds 1 except for 1g show antifungal activities against yeasts and filamentous fungi in vitro, especially (+)-1f have equal or superior activities compared to those of itraconazole.

Antifungal Agents↗
PubMed1999

Mouse endostatin inhibits the formation of lung and liver metastases.

Angiogenesis is required for tumor formation. Several studies have demonstrated that tumor angiogenesis is regulated by a balance between proangiogenesis and antiangiogenesis factors and that this balance varies in different organ environments. To investigate whether expression of an angiogenesis inhibitor by cancer cells could alter this balance and prevent tumor formation in different organ environments, we engineered stable transfectants from RenCa mouse renal carcinoma cells and SW620 human colon carcinoma cells to constitutively secrete a mouse endostatin protein with c-myc and polyhistidine (His) tags. Production and secretion of the endostatin-c-myc-His fusion protein by endostatin-transfected cells were confirmed by immunofluorescence staining and Western blot analysis. The endostatin transfectants and control transfectants, stably transfected with a control plasmid, had similar in vitro growth rates compared with their parental cell lines. Conditioned medium from endostatin-transfected cells inhibited human umbilical vein endothelial cell proliferation by 36-51% compared with conditioned medium from control cells. After inoculation into mice, flank tumors from endostatin-transfected cells were 73-91% smaller than flank tumors from control cells after 3 weeks. Inoculation of a cell mixture containing 25% endostatin-transfected cells and 75% control cells resulted in inhibition of flank tumor formation as effective as after inoculation of 100% endostatin-transfected cells. Formation of lung metastases by RenCa endostatin-transfected cells and formation of liver metastases by SW620 endostatin-transfected cells were dramatically inhibited compared with formation of metastases by control cells. These findings demonstrate that endostatin can inhibit tumor formation in different organ environments and that gene delivery of endostatin into even a minority of tumor cells may be an effective strategy to prevent progression of micrometastases to macroscopic disease.

Animals↗
PubMed1999

Type I interferons (IFNs) regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression on human T cells: A novel mechanism for the antitumor effects of type I IFNs.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a proapoptotic member of the TNF family of type II membrane proteins, which constitutes one component of T cell cytotoxicity. In this study, we investigated the expression and function of TRAIL in human peripheral blood T (PBT) cells. Although freshly isolated PBT cells did not express a detectable level of TRAIL on their surface, a remarkable TRAIL expression was rapidly induced on the surface of both CD4(+) and CD8(+) PBT cells upon stimulation with anti-CD3 monoclonal antibody and type I interferons (IFNs). This enhancement of TRAIL expression was a unique feature of type I IFNs (IFN-alpha and IFN-beta), and neither type II IFN (IFN-gamma) nor various other cytokines enhanced TRAIL expression on anti-CD3-stimulated PBT cells. Type I IFNs have been used for clinical treatment of renal cell carcinomas (RCCs), and we found that most RCC cell lines were susceptible to TRAIL-induced apoptosis. Type I IFNs substantially augmented cytotoxic activity of anti-CD3-stimulated PBT cells against RCC cell lines in a TRAIL-dependent manner. These results indicate a unique feature of type I IFNs to regulate TRAIL-mediated T cell cytotoxicity, which may be involved in the antitumor effects of type I IFNs against various tumors.

Antineoplastic Agents↗
PubMed1999

Involvement of CD44 in matrix metalloproteinase-2 regulation in human melanoma cells.

CD44 is a family of cell-surface-adhesion proteins that are thought to play an important role in cancer invasion and metastasis. However, the specific mechanisms by which CD44 expression modulates invasion or metastasis are not well understood. In the current study, we have demonstrated that treatment of human melanoma cells with a CD44 MAb, F10-44-2, induces up-regulation of matrix metalloproteinase-2 (MMP-2) protein and mRNA. Moreover, treatment of melanoma cells with MAb F10-44-2 enhances their migration through gelatin-coated membranes and invasion through reconstituted basement membranes. Treatment of melanoma cells with several known CD44 ligands, including hyaluronate, extracellular-matrix proteins, and osteopontin, did not induce MMP-2 production. CD44 binding by F10-44-2 MAb results in induction of MMP-2 expression, which is associated with enhanced cell migration and invasion. These findings have several implications for investigations into tumor metastasis, development, and lymphocyte function.

Antibodies, Monoclonal↗
PubMed1999

[Development and characterization of a monoclonal antibody which recognizes a new prostate-organ specific antigen].

PURPOSE: Development and characterization of monoclonal antibodies which recognizes a new prostate-organ specific antigen. METHOD: For development of monoclonal antibodies, hybrid cells were prepared by fusion of spleen cells of BALB/c mice immunized with the homogenates of surgically resected prostatic tissue and P 3 x Ag 8 U 1 (P 3 U 1) murine myeloma cells. Supernatants of hybrid clones were primarily screened using an ELISA on human prostatic cancer cell line PC-3 and human bladder cancer cell line T-24. In the secondary screening, they were tested on normal tissues by immunohistochemical staining. To characterize the antigens, biochemical analyses were performed using seminal plasma as an antigen by western blotting and gel filtration, and the reactivity of antibodies were compared with that of antibodies against prostatic acid phosphatase (PAP), prostate-specific antigen (PSA) and gamma-seminoprotein (gamma-Sm). RESULTS: A monoclonal antibody termed KP-9 was obtained and it only reacted with PC-3 and prostate tissues, but did not react with other cell lines and normal tissues. Immunohistochemical staining of prostate tissue revealed that KP-9 stained grandular epithelium and grandular exudate of normal and malignant prostatic tissues, and especially, strongly stained the apical site of grandular epithelium. Western blotting and gel filtration of seminal plasma suggested that the molecular weight of the KP-9 antigen was more than 300,000 and was different from PAP, PSA and gamma-Sm. CONCLUSION: We have developed a monoclonal antibody, KP-9 which specifically reacts with prostatic cancer as well as benign prostatic tissues. The antigen recognized by KP-9 appeared to be a new prostate-organ specific antigen and may be a useful marker for prostatic cancer such as PAP, PSA and gamma-Sm.

Animals↗
PubMed1998

Overexpression of Bcl-2 in bladder cancer cells inhibits apoptosis induced by cisplatin and adenoviral-mediated p53 gene transfer.

To investigate the effects of the expression of Bcl-2 protein in bladder cancer on the apoptosis induced by cisplatin or adenoviral-mediated p53 gene (Ad5CMV-p53) transfer, we transfected the bcl-2 gene into KoTCC-1, a human bladder cancer cell line that does not express the Bcl-2 protein. The Bcl-2-transfected KoTCC-1 (KoTCC-1/B) exhibited significantly higher resistance to both cisplatin and Ad5CMV-p53 transfer than did either the parental KoTCC-1 (KoTCC-1/P) or the vector-only transfected cell line (KoTCC-1/C). The flow cytometric analysis of the propidium iodide-stained nuclei and DNA fragmentation analysis after cisplatin or Ad5CMV-p53 treatment revealed DNA degradation in both KoTCC-1/P and KoTCC-1/C, whereas KoTCC1/B showed a marked inhibition of DNA degradation. Following the treatment with cisplatin or Ad5CMV-p53, the accumulation of p53 protein was highly detectable for a long period in KoTCC-1/B compared to that in KoTTC-1/P and KoTCC-1/C. Furthermore, the cisplatin and Ad5CMV-p53 treatments each reduced the volume of the subcutaneous tumors established in nude mice formed by KoTCC-1/P or KoTCC-1/C; in contrast, their reductive effects on the tumors formed by KoTCC-1/B were significantly suppressed. The intraperitoneal tumor cell implantation model revealed that the prognoses of mice injected with KoTCC-1/B were significantly inferior to those of the mice injected with either KoTCC-1/P or KoTCC-1/C after treatment with cisplatin or Ad5CMV-p53. These findings suggest that the expression of Bcl-2 in bladder cancer cells interferes with the therapeutic effects of cisplatin and Ad5CMV-p53 through the inhibition of the apoptotic pathway.

Adenoviruses, Human↗
PubMed1998

Recurrent annular erythema in a case of seronegative Sjögren's syndrome.

We describe a case of Sjögren's syndrome who repeatedly developed annular erythema on her extremities. Her anti-nuclear antibody, anti-SSA/Ro antibody, and anti-SSB/La antibody were all negative. Characteristics of the annular erythema included a tendency to appear on the extremities especially in summer, spontaneous regression after 1-2 weeks, and residual slight pigmentation. The histological findings revealed dermal perivascular lymphocytic infiltration admixed with some neutrophils. Slight exsudative changes were found in the upper dermis. There were no epidermal changes. This case suggests the existence of annular erythema which may not be related to the anti-SSA/Ro or anti-SSB/La antibody. Unknown factors other than those antibodies may be involved in the pathogenesis of the annular erythema.

Antibodies, Antinuclear↗
PubMed1998

Multifocal renal cell carcinoma in Japanese patients with tumors with maximal diameters of 50 mm. or less.

PURPOSE: We determined the risk of local recurrence in 64 Japanese patients a median of 69 years old with renal cell carcinoma who were possible candidates for nephron sparing surgery and who underwent radical nephrectomy. MATERIALS AND METHODS: A total of 64 kidneys in which tumors 50 mm. or less were resected were prospectively examined pathologically in 3 mm. sections. The incidence of satellite tumors and the relationship between the pathological findings of the primary and satellite tumors were evaluated. RESULTS: Satellite tumors were identified in 10 of the 64 kidneys (15.6%), a rate similar to that reported in the United States. The correlation of histological findings between primary and satellite tumors was 70% for tumor grade. Satellite tumor grade was less than that of the primary lesion in 3 cases. In 60% of the specimens with multifocal renal cancer satellite tumors were within 10 mm. of the margin of the primary tumor. At this distance, if partial nephrectomy had been performed, the satellite lesions would have been missed in 4 of these 10 patients (40%). Of the 10 kidneys with satellite renal tumors 8 (80%) had vascular invasion of the primary tumor. Multiple logistic regression analysis demonstrated that vascular invasion was a significant predictor of multifocality of renal cell carcinoma. CONCLUSIONS: Our results suggest that vascular invasion is a risk factor for multifocality in Japanese patients with renal cell carcinoma. Therefore, careful and long-term followup is necessary in patients with renal cell carcinoma who have undergone nephron sparing surgery, especially those with vascular invasion of the primary tumor.

Adult↗
PubMed1997

Percutaneous treatment of transitional cell carcinoma of the upper urinary tract.

BACKGROUND: We evaluated the long-term effect of percutaneous resection in 2 Japanese patients with transitional cell carcinoma of the renal pelvis, and reviewed the medical literature on similar patients, to determine the appropriate indications for percutaneous treatment of transitional cell carcinoma in the upper urinary tract. RESULTS: Indications for endoscopic resection in the 2 patients were renal insufficiency and unsuitability for major open surgery. The patients had no recurrence during follow-up. Seven previous reports described percutaneous resection of upper urinary tract transitional cell carcinoma in 82 patients. Although 72.6% of the patients were successfully treated by percutaneous resection, half of the patients with grade 3 carcinoma developed recurrence. CONCLUSION: These results, together with those of the 7 published reports, suggest that percutaneous resection should be limited to selected patients with low-grade transitional cell carcinoma.

Aged↗
PubMed1997

Basic fibroblast growth factor regulates matrix metalloproteinases production and in vitro invasiveness in human bladder cancer cell lines.

PURPOSE: This study was designed to investigate the effect of endogenous basic fibroblast growth factor (FGF-2) on matrix metalloproteinases (MMPs) production and in vitro invasive potential of human bladder cancer cell lines. MATERIALS AND METHODS: The human bladder cancer cell lines, HT1376 and KoTCC-1, were used in this study. The mRNA for FGF receptor has been shown to be expressed in both cell lines; the mRNA for FGF-2 is expressed in only KoTCC-1. The effects of FGF-2 expression on HT1376 by gene transfection and those of FGF-2 antisense oligonucleotides treatment on KoTCC-1 were analyzed by zymography and in vitro tumor cell invasion assay. RESULTS: The introduction of human FGF-2 gene into HT1376 cells markedly enhanced both the MMP-2 and MMP-9 production, and the in vitro invasive potential was also increased. In contrast, the exposure of KoTCC-1 cells to FGF-2 specific antisense oligonucleotides decreased the MMP-2 production and in vitro invasive potential, but the exposure to FGF-2 sense oligonucleotides did not. CONCLUSIONS: These findings suggest that FGF-2 plays an important role in the invasive process of human bladder cancer in part through the regulation of MMPs production.

Cell Division↗
PubMed1996

NF-kappa B is induced in the nuclei of cultured rat aortic smooth muscle cells by stimulation of various growth factors.

We investigated whether induction of transcription factor NF-kappa B is involved in the proliferation of cultured rat aortic smooth muscle cell using electrophoretic mobility shift assay and immunocytochemistry. NF-kappa B was induced in the nucleus in a dose-dependent manner when the smooth muscle cells were stimulated by various growth factors such as PDGF-BB, bFGF, EGF and IGF-1, but not growth inhibitors such as TGF-beta and IFN-gamma. Among growth factors, PDGF-BB and bFGF, more potent growth stimulators, induced higher kappa B binding activity than EGF or IGF-1. These evidences were also supported by the results obtained with immunocytochemistry. Immunocytochemistry also showed that the induced NF-kappa B contained p50 and p65. These results suggest that NF-kappa B induction may be involved in the proliferation of vascular smooth muscle cell.

Animals↗
PubMed1996

Messenger ribonucleic acids for fibroblast growth factors and their receptor in bladder and renal cell carcinoma cell lines.

FGF-like growth factors have been detected in the urine of patients with bladder or renal cell carcinoma. FGF-1-like and FGF-2-like proteins have been detected in the urine of patients with bladder carcinoma. However, the expression of FGFs and their receptor in bladder and renal cell carcinoma cells remains limited. We measured the mRNA levels of FGFs and their receptor in these carcinoma cell lines by means of RT-PCR. We detected FGF-8 mRNA expression in murine cell lines of bladder and renal cell carcinomas but not in those of the normal bladder and kidney. Furthermore, FGF-8 mRNA expression was detected in all human bladder and renal cell carcinoma cell lines tested. We also frequently detected FGF-1, FGF-2 and FGF-5 mRNA expression in human bladder and renal cell carcinoma cell lines. These results indicate that FGF-8 is also candidate for marker of these types of carcinoma as well as FGF-1 and FGF-2.

Animals↗
PubMed1996

Introduction of basic fibroblast growth factor gene into mouse renal cell carcinoma cell line enhances its metastatic potential.

To clarify the role of basic fibroblast growth factor (FGF-2) in the malignant progression of renal cell carcinoma, we transfected the FGF-2 gene, which lacks the typical signal sequence, into RenCa, a mouse renal cell carcinoma cell line that does not express FGF-2 mRNA. In an in vitro tumor cell invasion assay, the FGF-2-transfected cell lines (RenCa/F) exhibited 3- to 4-fold higher invasive potential than either the parental RenCa (RenCa/P) or the vector-only transfected cell line (RenCa/C). Zymography showed a marked increase in matrix metalloproteinase 2 (MMP-2) production in the culture supernatants of RenCa/F. Furthermore, when injected i.v. or into the renal subcapsule in syngeneic mice, RenCa/F formed more than 10 times as many metastatic nodules in the lung as did RenCa/P and RenCa/C. Metastases to the liver and mesenteric lymph nodes were observed only after the injection of RenCa/F into the renal subcapsule. In contrast, there was no significant difference in either cell proliferation in vitro or tumor growth in vivo among RenCa sublines. These results suggest that if it is overexpressed, endogenous native FGF-2 plays an important role in the invasion and metastasis of renal cell carcinoma, probably through the production of MMP-2.

Animals↗