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Biomedical subjects

A Hongo

Publications and source records attributed to A Hongo.

At least 37 records · Page 2Linked to original sources
PubMed1999

Angiogenesis and platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in cervical cancer.

The object of this study was to clarify the association of platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (dThdPase), separately assessed in cancer cells and in stroma cells, with clinicopathological factors including tumor angiogenesis and prognosis in cervical cancer. The expression of PD-ECGF was evaluated by immunohistochemical staining in 92 patients with stage Ib-II cervical cancer. The microvessel count was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area. Microvessel count was significantly higher in tumors with non-squamous cell carcinoma. PD-ECGF expression in cancer cells was significantly higher in tumors with pelvic node metastasis and squamous cell carcinoma. Immunopositivity for PD-ECGF in stroma cells was significantly higher in tumors with large size and deep stromal invasion. The microvessel counts in cases with positive PD-ECGF expression in stroma cells were significantly higher than those in cases with negative PD-ECGF expression in stroma cells (p=0.048). Disease-free survival and overall survival were significantly worse in patients with deep stromal invasion, parametrial involvement, vaginal involvement, lymph-vascular space involvement, pelvic lymph node metastasis and high microvessel count. A multivariate analysis using Cox's proportional hazard model showed that high microvessel count independently predicted disease-free and overall survival. The expression of PD-ECGF in stroma cells may play a crucial role in the promotion of angiogenesis and tumor angiogenesis can be used as a useful prognostic marker for cervical cancer.

Adult↗
PubMed1999

Angiogenesis and platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in endometrial cancer.

The object of this study was to clarify the association of angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (dThdPase) with clinicopathological factors including tumor angiogenesis and patient outcome in endometrial cancer. There was no correlation between the expression of PD-ECGF in cancer cells and any of the clinicopathological variables. Immunopositivity for PD-ECGF in stroma cells was significantly higher in poorly differentiated adenocarcinomas. The microvessel counts correlated with PD-ECGF positive stroma cells (p<0.0001). Disease-free survival was significantly worse in patients with marked PD-ECGF expression in stromal cells and high microvessel count. A multivariate analysis using Cox's proportional hazard model showed that high microvessel counts independently predicted disease-free survival as well as stage and myometrial invasion. The expression of PD-ECGF in stroma cells may play a crucial role in the promotion of angiogenesis. Tumor angiogenesis can be used to predict prognosis in patients with endometrial cancer.

Adenocarcinoma↗
PubMed1999

[Neoadjuvant chemotherapy for advanced cervical cancer].

Twenty-five patients with advanced cervical cancer (IIb-IVa) were treated with neoadjuvant chemotherapy followed by radical hysterectomy or radiotherapy. According to the evaluation by MRI, complete response was achieved in 2 cases and partial response in 17 cases. Eventually the response rate was 76%. The response rate was higher in squamous cell carcinomas (85%) than adenocarcinomas or adenosquamous carcinomas (67%). The histological effect is superior in squamous cell carcinomas than adenocarcinomas or adenosquamous carcinomas. Radical hysterectomy was performed in 5 cases of 11 (45%) stage III-IVa cervical cancers. There was no correlation between tumor size and response to NAC. NAC therapy may be useful therapy in advanced cervical cancers, especially squamous cell carcinomas.

Adenocarcinoma↗
PubMed1998

Inhibition of tumorigenesis and induction of apoptosis in human tumor cells by the stable expression of a myristylated COOH terminus of the insulin-like growth factor I receptor.

The insulin-like growth factor I receptor (IGF-IR) plays an important role in cell transformation and in protection from apoptosis. Although the wild-type IGF-IR generally has an antiapoptotic effect, there are reports that its COOH terminus may actually generate a proapoptotic signal. Three different expression plasmids, all coding for the COOH-terminal sequences of the human IGF-IR, MyCF, CF, and MyKCF, were stably transfected into human ovarian carcinoma CaOV-3 cells. All three plasmids had no effect on monolayer growth but strongly inhibited colony formation in soft agar. Only one of the plasmids, MyCF, expressing the last 112 amino acids of the IGF-IR and carrying a myristylation signal, caused large-scale apoptosis of CaOV-3 cells in vivo and abrogation of tumorigenesis in nude mice. The plasmid expressing the MyCF sequence was also introduced into human glioblastoma T98G cells, where it decreased the clonogenicity of cells, caused a marked inhibition of colony formation in soft agar, and induced apoptosis in vivo. A double mutation at residues 1293 and 1294 of MyCF completely abrogated its inhibitory and proapoptotic activities. Neither the autophosphorylation of the IGF-IR nor the tyrosyl phosphorylation of IRS-1 was affected by the expression of the MyCF plasmid. These and other findings suggest that a stably expressed myristylated COOH terminus of the IGF-IR can induce apoptosis in human tumor cells in vivo and inhibit tumorigenesis in nude mice by a mechanism that avoids the protective effect of the IGF-IR.

Animals↗
PubMed1998

Ecabet sodium, a locally acting antiulcer drug, inhibits urease activity of Helicobacter pylori.

In order to clarify the mechanism of the anti-Helicobacter pylori action of ecabet sodium (ecabet), a locally acting antiulcer drug, we evaluated the effects of ecabet on H. pylori urease activity in vitro. H. pylori was cultured and a crude preparation of urease was made. Urea-dependent survival of H. pylori at acid pH was significantly inhibited by ecabet. The urease activity of intact cells and a crude enzyme preparation from H. pylori had two pH optima: pH 4.5-5.0 and 8.0. Ecabet (1-4 mg/ml) concentration dependently inhibited the urease activity of both preparations at pH 5.0, but there was no inhibition at pH 8.0. The enzyme activity was inhibited by ecabet gradually and was not restored by dilution, in contrast to the inhibition elicited by benzohydroxamic acid, a specific and reversible urease inhibitor. These results suggest that irreversible inhibition of H. pylori urease activity contributes to the anti-H. pylori action of ecabet.

Abietanes↗
PubMed1998

Presence of human papilloma virus DNA in pelvic lymph nodes can predict unexpected recurrence of cervical cancer in patients with histologically negative lymph nodes.

Patients without any evidence of lymph node metastases are supposed to have a fair prognosis, but some of these patients develop recurrent disease unexpectedly after surgery. The object of this study is to examine whether the detection of human papilloma virus (HPV) DNA could be used as a diagnostic marker to predict such recurrences. Two hundred and thirty-six patients undergoing radical hysterectomy and pelvic lymphadenectomy for stage Ib and II cervical cancer at Okayama University Hospital (Japan) from 1988-1994 were reviewed, and only those cases positive for HPV-16 or HPV-18 in primary sites were included in this survey. The E6-E7 region of the HPV genome was amplified by a sensitive nested PCR from archival pelvic lymph node specimens. HPV sequences identical to those of the primary sites were detected in histologically confirmed negative lymph nodes, regardless of histological type or HPV type of the primary lesion, in 9 of 10 patients who recurred within 4 years of surgery. In contrast, histologically confirmed negative lymph nodes from 12 patients with stage IIb disease without evidence of recurrent disease were all negative for the presence of HPV, except for 1 lymph node. The presence of HPV DNA in histologically negative nodes implies the possibility of early nodal involvement or coexistence of undetectable hematogenic dissemination and could therefore be used as a diagnostic marker to predict the unexpected recurrence of these patients.

Adult↗
PubMed1997

The IGF-I receptor in mitogenesis and transformation of mouse embryo cells: role of receptor number.

The type 1 receptor for insulin-like growth factors (IGF-IR) plays an important role in the growth and transformation of several types of cells. We have investigated the role of IGF-IR number in IGF-I-mediated mitogenesis and transformation of mouse embryo fibroblasts. We have used R- cells (3T3-like cells originating from mouse embryos with a targeted disruption of the IGF-IR genes) transfected with a plasmid expressing the human IGF-IR cDNA to generate clones with receptor numbers ranging from zero to 10(6) receptors per cell. In this model, between 15,000 and 22,000 receptors per cell are sufficient to render mouse embryo cells competent to grow in serum-free medium supplemented solely with IGF-I. For growth in soft agar, 30,000 receptors per cell seem to be the minimum requirement. These experiments indicate that a small increment in the number of receptors per cell, well within the physiological range, can modulate the mitogenic and transforming activities of the IGF-IR in 3T3-like cells.

3T3 Cells↗
PubMed1997

The insulin-like growth factor I receptor as a physiologically relevant target of p53 in apoptosis caused by interleukin-3 withdrawal.

The wild-type p53 protein is known to modulate apoptosis induced in 32D murine hemopoietic cells by interleukin-3 withdrawal. In 32D cells and in 32D cells constitutively expressing a temperature-sensitive mutant of p53 (32Dtsp53), overexpression of a wild-type (but not a mutant) insulin-like growth factor I receptor (IGF-IR) protects these cells from apoptosis. A tsp53 in its wild-type conformation causes a decrease in the levels of IGF-IRs, and this decrease is accompanied by increased sensitivity of these cells to apoptosis. However, when the expression of the IGF-IR cDNA is regulated by a viral promoter, IGF-IR levels are not decreased by a wild-type p53, and apoptosis does not occur. These findings show that, in 32Dtsp53 cells, the IGF-IR is a physiologically relevant target of p53 in the process of apoptosis.

Animals↗
PubMed1996

Mutational analysis of the mitogenic and transforming activities of the insulin-like growth factor I receptor.

THe type 1 insulin-like growth factor receptor (IGF-IR) plays an important role in mitogenesis and transformation. It has been previously shown that mitogenic signaling and transforming activity of the IGF-IR can be dissociated: a receptor truncated at residue 1229 (C-terminus) is fully mitogenic, in terms of its response to IGF-I, but cannot transform 3T3-like cells that are devoid of endogenous IGF-IRs (R- cells). We have extended our mutational analysis of the C-terminus of the human IGF-IR, by stably transfecting several mutant receptors into R- cells, and testing the resulting cell lines for IGF-I-mediated mitogenic response and formation of colonies in soft agar. The results indicate that the transforming domain of the IGF-IR can be localized between residues 1245 and 1310, these sequences being not required for mitogenic signaling. Within these residues, there are at least two areas that contribute to the transforming activity of the receptor.

3T3 Cells↗
PubMed1996

The role of Grb2 in the growth and transformation of mouse embryo cells.

An overexpressed insulin-like growth factor I receptor (IGF-IR) allows cells to grow in IGF-I only and to form colonies in soft agar. Conversely, cells with a targeted disruption of the IGF-IR genes, R- cells, are refractory to transformation by several oncoproteins and growth factor receptors, that readily transform their wild type counterparts, W cells. Grb2 is an SH2-SH3 domains protein that links tyrosine kinase receptors to ras signalling. In order to determine its role in mitogenesis and transformation, we have transfected a plasmid expressing Grb2 into R- and W cells, and their derivatives already expressing the SV40 large T antigen. In addition, we have used loss-of-function mutants of Grb2 to inquire whether they would act as dominant negatives. Our results show that: (1) an overexpressed Grb2 cannot replace the IGF-IR in IGF-I-mediated mitogenesis; (2) Grb2 also fails to transform either W or R- cells; (3) Grb2 and SV40 T antigen, singly transfected, cannot transform R- cells, but can do so when combined; and (4) SH3 domain mutants of Grb2 act as dominant negatives, causing reversion of the transformed phenotype. We conclude that Grb2 is necessary but not sufficient for transformation.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Acylated pelargonidin 3-sambubioside-5-glucosides in Matthiola incana.

Ten acylated pelargonidin 3-sambubioside-5-glucosides were isolated from the red-purple flowers of Matthiola incana, and also pelargonidin 3-glucoside was isolated from the brownish-red flowers of this plant. FAB mass measurements of 10 acylated anthocyanins gave their molecular ions [M]+ at 903-1195 m/z, which were based on acylated pelargonidin 3-sambubioside-5-glucosides with malonic acid, sinapic acid, p-coumaric acid, caffeic acid and/or ferulic acid. This was confirmed by the analysis of NMR spectra and the experiments of acid and alkaline hydrolysis. By spectral and chemical methods, seven of the 10 pigments were determined to be pelargonidin 3-O-[2-O-(2-O-(acyl-I)-beta-D-xylopyranosyl)- 6-O-(acyl-II)-beta-D-glucopyranoside]-5-O-[6-O-(malonyl)-beta-D- glucopyranoside], in which acyl moieties varied between sinapic, ferulic, caffeic and p-coumaric acids. The occurrence of these pigments was examined in 10 red-purple, 10 salmon-pink, three apricot and three copper colour cultivars of M. incana by HPLC. The acylated pelargonidin 3-sambubioside-5-glucosides were present as the dominant pigments in the red-purple, salmon-pink and apricot colour cultivars. On the other hand, pelargonidin 3-glucoside was present as a dominant anthocyanin in the copper colour cultivars and also pelargonidin 3-sambubioside-5-glucoside was confirmed by HPLC as a minor pigment in the copper colour flowers.

Acylation↗
PubMed1995

Bacterial activity of a new antiulcer agent, ecabet sodium, against Helicobacter pylori under acidic conditions.

Helicobacter pylori NCTC 11637, which is nonviable at pH 3.0, became viable after addition of 10 mM urea owing to ammonia production by urease. In a buffer supplemented with urea, ecabet sodium decreased both the production of ammonia and the number of viable cells of H. pylori NCTC 11637 and changed the bacteria from the bacilliform to the horseshoe or doughnut shape in a concentration-dependent manner. In particular, ecabet sodium (2 and 4 mg/ml) decreased the number of viable cells below the control level. Benzohydroxamic acid, a urease inhibitor, also caused a decrease in ammonia production accompanied by a decrease in the number of viable cells and changed the morphological form at pH 3.0, but the number of viable cells was not lowered below the control level. In buffers at various pHs without urea, ecabet sodium showed a concentration-dependent bactericidal effect on H. pylori at pHs 4.0 and 5.0 but not at pHs 6.0 and 7.0 while benzohydroxamic acid caused only a slight decrease in the number of viable cells at pH 4.0. These results suggest that ecabet sodium has strong bactericidal activity in addition to its urease-inhibiting activity under acidic conditions.

Abietanes↗
PubMed1995

Mechanism of anti-urease action by the anti-ulcer drug ecabet sodium.

To investigate the mechanism of the anti-urease action of ecabet sodium (ecabet) observed in Helicobacter pylori in vitro, the effects of ecabet on purified urease from jack bean were studied in comparison with the effects of the specific urease inhibitor benzohydroxamic acid (BHA). After incubation of the enzyme with the test drug for a period of time, urease activity was measured. Ecabet depressed the activity below pH 5, and the lower the pH, the greater the degree of depression. The degree of depression by ecabet increased gradually during incubation and reached a plateau in 20 min, whereas that by BHA attained a maximum rapidly. The IC50 values of ecabet and BHA were 2.1 mg/ml and 0.5 microgram/ml, respectively. When the incubation mixture of urease with an inhibitor was diluted and further incubated, the depressed activity by BHA reverted gradually, but that by ecabet did not. When the incubation mixture of urease with ecabet was centrifuged, the urease activity of the mixture decreased in parallel with the reduction in protein concentration of the supernatant. When the incubation mixture of urease and 14C-ecabet was ultrafiltered to remove the drug, the radioactivity in the retentate remained in parallel with the degree of reduction of urease activity in the retentate. These results indicate that ecabet irreversibly depresses the urease activity of jack bean, and suggest that the depression is caused by irreversible binding of ecabet to urease followed by denaturation of the enzyme protein.

Abietanes↗
PubMed1994

A comparison of in vitro platinum-DNA adduct formation between carboplatin and cisplatin.

DNA damage induced by carboplatin [cis-diammine-(1, 1-cyclobutanedicarboxylato)platinum(II)] was studied in vitro in comparison with cisplatin [cis-diammine-dichloroplatinum(II)]. The drug-induced DNA damage monitored by conformational change of pUC18 plasmid DNA showed that carboplatin required 10 times higher drug concentration and 7.5 times longer incubation time than those of cisplatin to induce the same degree of conformational change on plasmid DNA. The carboplatin-induced DNA damage was promoted by the increase of pH of the reaction mixture for platinum-DNA adduct formation. Sequence gel analysis of carboplatin-damaged DNA indicated that carboplatin attacked preferentially the sequence of GG >> AG > GA > GNG in the order, similarly to the case of cisplatin. DNA adducts formed by carboplatin were analyzed by HPLC after a sequential digestion of carboplatin-treated DNA with deoxyribonuclease I and S1 nuclease. A single peak having the same retention time as that of bifunctional adduct of (dGMP)2Pt(NH3)2 appeared by treating DNA with carboplatin. The adduct was assigned to be d(pGpG) > Pt(NH3)2. These results suggested that carboplatin induces the same platinum-DNA adducts as those induced by cisplatin, and that the difference in efficiency or kinetics of DNA damage between carboplatin and cisplatin is due to difference of aquation rate between them.

Base Composition↗
PubMed1993

Inhibition of cisplatin-mediated DNA damage in vitro by ribonucleotides.

Effects of ribonucleotides on cis-diamminedichloroplatinum(II) (cisplatin)-mediated DNA damage were studied by incubating pUC18 DNA with cisplatin in the presence of nucleotide, and by monitoring conformational change and sensitivity change to restriction enzyme HpaII of the DNA due to the platinum-DNA adduct formation. The cisplatin-mediated DNA damage was inhibited in a dose-dependent fashion by ATP or GTP, substantially at their physiological intracellular concentrations, and almost completely by 5 mM ATP or 2 mM GTP. The inhibitory effect of nucleotide on the platination of DNA was in the order of GTP > ATP >> CTP > UTP, and of nucleoside triphosphate > nucleoside diphosphate > nucleoside monophosphate. Nucleoside did not show any significant effect on platination of DNA. To elucidate the mechanism of the nucleotide effects on platination of DNA, interaction between ATP or GTP and cisplatin was analyzed by high-performance liquid chromatography. The results suggested that ATP inhibits cisplatin-mediated DNA damage both by forming a platinum-ATP adduct and by non-covalent ionic interaction with cisplatin, while GTP acts largely by forming platinum-GTP adducts.

Cisplatin↗
PubMedDate not supplied

Heparanase expression in both normal endometrium and endometrial cancer.

The aim of this study was to investigate the relationship between heparanase expression and prognostic factors in endometrial cancer, as well as the relationship between heparanase expression during phases of the normal endometrial cycle. Immunohistochemical analysis of 166 endometrial cancers and 34 normal endometria in various phases of growth was performed. The heparanase expression in the late-proliferative phase of normal endometria was found to be significantly higher than in either the early-proliferative or the secretory phases (P= .012 and P= .044, respectively). Heparanase expression was also significantly higher in endometrial cancer patients with tumors of an advanced FIGO stage (P= .0003) and high FIGO grade (P= .004) and with cancers showing either deep myometrial invasion (P= .023), lymph node metastasis (P= .006), lymphvascular space involvement (P= .048), or positive peritoneal cytology (P= .010). The disease-free and overall survival rates of patients with intense heparanase expression were significantly lower than those of patients with absent or moderate heparanase expression (P= .004 and P= .002, respectively). Heparanase may participate in normal endometrial remodeling and can serve as an indicator of the aggressive potential and poor prognosis of endometrial cancers.

Adult↗