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Biomedical subjects

T Furui

Publications and source records attributed to T Furui.

At least 19 recordsLinked to original sources
PubMed2006

Gi protein-mediated translocation of serine/threonine phosphatase to the plasma membrane and apoptosis of ovarian cancer cell in response to gonadotropin-releasing hormone antagonist cetrorelix.

Serine/threonine protein phosphatase 2A (PP2A), a crucial enzyme in apoptosis control, has been demonstrated within the plasma membrane as well as in the soluble fraction. This study aimed to examine hormonal translocation of PP2A to the plasma membrane in gonadotropin-releasing hormone (GnRH)-responsive ovarian cancer cells. Apoptosis of ovarian cancer cell lines Caov-3 and SK-Ov-3 was quantified by nuclear morphology after staining with Hoechst 33342 dye. PP2A protein and activity in plasma membrane were assessed by immunohistochemical staining with PP2A-specific antibodies and by the measurement of the dephosphorylation of phosphopeptide highly selective for the PP2A, respectively. Incubation for 48 h with a GnRH antagonist cetrorelix caused parallel increases in the percentage of cells undergoing apoptosis and the membrane-associated PP2A activity; half-maximal effects occurred with 5 nmol/l cetrorelix. PP2A protein was also localised to the plasma membrane when the cell lines were exposed to cetrorelix. Pretreatment of the cells with pertussis toxin, but not cholera toxin, completely inhibited cetrorelix-stimulated apoptotic cell death and PP2A redistribution. These findings demonstrate that translocation of PP2A to plasma membrane is closely coupled to the onset of apoptosis in ovarian cancer cells exposed to GnRH antagonist. These GnRH-induced cellular events may be mediated through pertussis toxin-sensitive Gi protein-linked GnRH receptor.

Apoptosis↗
PubMed2003

Treatment of perimenopausal women with uterine myoma: successful use of a depot GnRH agonist leading to a natural menopause.

Gonadotrophin-releasing hormone agonists (GnRHa) reduce the size of uterine fibroids and relieve patients of myoma-related symptoms. However, rapid regrowth frequently occurs after the therapy is stopped. We attempted to determine whether GnRHa therapy could lead perimenopausal women carrying symptomatic myomas to the natural onset of the menopause. A retrospective analysis of 145 patients who received GnRHa for 24 weeks demonstrated that after cessation of therapy no menstruation occurred over 25 weeks in women aged over 45 years, with elevated levels of follicle-stimulating hormone (FSH) and luteinising hormone (LH) > 25 mIU/ml. To extend this study, we studied prospectively 21 women, aged 45 years and older who had regular menstruation with symptoms attributed to myomas and elevated days 3 - 5 FSH and days 3 - 5 LH levels ( > 25 mIU/ml). After discontinuation of GnRHa (leuprorelin acetate, 1.88 mg) therapy for 6 months, menstruation occurred in only two of 21 individuals but the remaining 19 cases had no menstrual bleeding. It is suggested from this study that the rise in early follicular phase serum gonadotrophins, in particular FSH > 25 mIU/ml, may precede the natural menopause following (or during) GnRHa therapy in older women. Measuring days 3 - 5 serum FSH concentrations may make it easier to decide on the optimal duration of therapy for symptomatic uterine fibroids in perimenopausal women aged > 45 years.

Adult↗
PubMed2003

Magnetic resonance imaging in the evaluating of double uterus and associated urinary tract anomalies: a report of five cases.

Uterine anomalies are associated with unilateral renal aplasia. We present the MR features of five cases with 'double' uteri. The anomalies consisted of four cases of uterus didelphys and one of a complete septate uterus. All the cases with uterus didelphys also had a longitudinal vaginal septum. The MR diagnoses were confirmed with hysterosalpingography and with laparoscopy. In one case of didelphic uterus, MR images predicted the (three-dimensional helical) computer tomography (CT)-pyelographic diagnosis of renal aplasia in which the single kidney was normal. The study shows that MR is a valuable tool for the diagnosis of not only uterine anomalies but also associated anomalies in other systems.

Abnormalities, Multiple↗
PubMed2003

Gonadotrophin-releasing hormones agonist therapy increases peritoneal fibrinolytic activity and prevents adhesion formation after myomectomy.

The aim of this study was to evaluate uterine adhesions after myomectomy and peritoneal fibrinolytic capacity in women treated with gonadotrophin-releasing hormone agonist (GnRHa) before surgery. A prospective observational study comprised 15 infertile women who underwent myomectomy. Before surgery, 10 were treated with buserelin acetate (900 microg/day) for 10-12 weeks followed by additional postoperative treatment with GnRHa for 4 weeks (GnRHa group) and five received no treatment (control group). Peritoneal fluid specimens were taken at the beginning of myomectomy and the adhesions were estimated by second-look surgery (caesarean section or laparoscopy). Levels of plasminogen activator (PA) and PA inhibitor (PAI) were determined by enzyme-immunosorbent assays. Pre- and postoperative GnRHa therapy significantly reduced adhesion formation compared with control groups (adhesion scores; 0.2 +/- 0.4 vs. 2 +/- 1, P<0.0001). GnRHa group showed a significant decrease in PAI level (P<0.0001) but no significant change in PA level, suggesting increased fibrinolytic capacity in peritoneal fluid from GnRHa-treated patients. These data suggest that GnRHa therapy is successful in preventing adhesion formation after myomectomy. GnRHa-induced shift to more fibrinolytic activity, mainly because of a decreased level of PAI, may play a critical role in the mechanism of the GnRHa's action on postoperative adhesion development.

Adult↗
PubMed2001

Comparative genomic hybridization analysis of genetic aberrations associated with development and progression of biliary tract carcinomas.

BACKGROUND: Little is known about genetic aberrations associated with development and progression of biliary tract carcinomas. METHODS: To study chromosomal aberrations associated with development and progression of biliary tract carcinomas, the authors used comparative genomic hybridization to examine 50 such carcinomas. RESULTS: Gains in part or in whole of chromosomes 1q, 8q, and 20q and losses of 5q, 8p, 9p, and 18q were detected frequently in early stage (T1/T2 classification) biliary tract carcinomas (> or = 40% of 19 early stage tumors), and they also were found in advanced stage (T3/T4 classification) tumors. In particular, loss of 9p was the most frequently observed aberration in both early stage (15 of 19; 78%) and advanced stage tumors (21 of 31; 68%). The frequencies of gains of 7p12-p14 (P < 0.003), 7p21-pter (P < 0.007), and 7q31 (P < 0.01) differed significantly between biliary tract carcinoma with and without distant metastasis. Also, gains of 5p and 19q13 and loss of 6q14-q16 were more frequent in tumors with lymph node metastasis than in those without it (P < 0.02). CONCLUSIONS: It is likely that loss of 9p is one of the genetic aberrations critical for the development of biliary tract carcinoma, whereas gains of 5p, 7p, 7q, and 19q and loss of 6q are considered later events associated with tumor progression and are thought to confer metastatic potential to biliary tract carcinomas.

Adult↗
PubMed2001

Gynecologic tumors and symptoms in childhood and adolescence.

Although tumors are rarely seen in girls, they should be considered in differential diagnosis because of the high incidence of potential malignancy in genital tumors compared with adults. Ultrasonography can quickly evaluate the underlying cause of genital symptoms or signs and allow timely intervention, while magnetic resonance imaging accurately measures the extent and location of the vaginal lesion. As a result of modern progress in the chemotherapy regimens, the prompt and precise detection of either benign or malignant tumors can lead to both cure and preservation of fertility with conservative surgery whenever possible. With the widespread use of obstetrical ultrasonography, fetal abdominal tumors are being diagnosed with increasing frequency. Most of these tumors will undergo spontaneous resolution within the first few months of life.

Adolescent↗
PubMed2000

Lysophosphatidic acid prevents apoptosis in fibroblasts via G(i)-protein-mediated activation of mitogen-activated protein kinase.

Lysophosphatidic acid (LPA) is a naturally occurring phospholipid with multiple biological functions. In the present study, we demonstrate that, besides its mitogenic activity, LPA is a potent survival factor, preventing serum-deprivation-induced apoptosis in fibroblasts and other cell types. Both the proliferative effect and survival activity of LPA are sensitive to the action of pertussis toxin (PTX), indicating that both processes are mediated by G(i) protein(s). We therefore focused on the role of G(i)-protein-mediated signalling events in the promotion of cell survival by LPA. In addition to activation of mitogen-activated protein kinase (MAPK), LPA stimulates a modest PTX-sensitive phosphorylation/activation of the serine/threonine kinase Akt, a survival mediator downstream of phosphoinositide 3-kinase (PI3K). Inhibition of PI3K with LY 294002 or wortmannin resulted in a marked inhibition of LPA-induced DNA synthesis, and yet the survival activity of LPA decreased by only 20-30%, suggesting a limited input of the PI3K-Akt cascade in LPA-induced cell survival. In contrast, inhibition of MAPK activation by the MEK-1 inhibitor, PD 98059, blocked both the proliferative and survival effects of LPA. These results indicate that LPA promotes cell survival largely via G(i)-protein-mediated activation of ERK1/ERK2, or other PD 98059-sensitive member(s) of the MAPK family.

3T3 Cells↗
PubMed2000

Differential efficacy of gonadotropin-releasing hormone (GnRH) agonist treatment on pedunculated and degenerated myomas: a retrospective study of 630 women.

This study was designed to compare the anatomical location of myomas (submucous, intramural, subserous, or cervical), whether pedunculated or non-pedunculated if degenerated or undegenerated and relating these findings to myoma volume reduction in women treated with gonadotropin-releasing hormone agonist (GnRHa). Our retrospective study group included 630 patients with symptoms attributed to fibroids. They were treated with a single GnRH agonist for 20 weeks and the size of the myoma was monitored by magnetic resonance imaging and/or ultrasonographic scan. During a 20 week-treatment, submucous, intramural, or subserous fibroids showed an overall reduction of 63% (P<0.01) with little variation between these types. No reduction in size was seen in cases of pedunculated, degenerated, or cervical myomas. These data suggest that GnRH agonist therapy might be used primarily for non-pedunculated and undegenerated myomas.

Journal Article↗
PubMed2000

Calcium concentration and artificial precipitates in human pancreatic juice.

We studied the role of the increase in the calcium concentration in pure pancreatic juice of alcoholic noncalcified chronic pancreatitis. Pure pancreatic juice was obtained endoscopically. The pancreatic juice from patients with chronic pancreatitis was adjusted to pH 7.5; then the calcium concentration was adjusted to 0.4, 2.9, 5.4, or 10.4 mmol/L. Artificial precipitates were produced by incubation of the samples at 37 degrees C for 6 hours. Proteins in the artificial precipitates were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the protein patterns were compared with the patterns of natural protein plugs from patients with chronic pancreatitis. The amount of the precipitate increased as the added calcium increased. The protein patterns of SDS-PAGE of the artificial precipitates were similar to those of protein plugs. Albumin, a-amylase, lipase, trypsinogen, and chymotrypsinogen were identified by immunoblotting both in the precipitate and in the protein plug. The increased calcium concentrations in pancreatic juice induced the formation of precipitates whose protein composition was similar to that of protein plugs. An increased calcium concentration in human pancreatic juice may play an important role in the pathogenesis of protein plugs.

Adult↗
PubMed2000

Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer.

Levels of lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) are elevated in the plasma and ascites of ovarian cancer patients, but not in most other tumor types. LPA increases cell proliferation, cell survival, resistance to cisplatin, cell shrinkage, and production of vascular endothelial growth factor, urokinase plasminogen activator, and LPA itself in ovarian cancer cells, but not in normal ovarian surface epithelial cells. PSP24 and members of the endothelial differentiation gene (EDG) family (EDG1, EDG2, EDG4, and EDG7) of G protein-coupled receptors mediate LPA signaling. Ovarian cancer cell lines do not express EDG1 mRNA, have variable EDG2 mRNA and protein levels, and frequently exhibit levels of EDG4 mRNA and protein, suggesting that EDG4 may contribute to the deleterious effects of LPA in ovarian cancer. In contrast, activation of the EDG2 LPA receptor on ovarian cancer cells may lead to apoptosis and counter the effects of other LPA receptors. Thus, the development of agonists and antagonists for the appropriate spectrum of LPA receptors may alter proliferation, apoptosis, or response to therapy of ovarian cancer cells. Indeed, over 60% of all current drugs target the G protein-coupled family of receptors, making the LPA receptor family a "drugable" target. LPC, although not as thoroughly studied, increases cellular proliferation and mediates multiple other functions through unique signaling pathways.

Ascites↗
PubMed2000

A gonadotropin-releasing hormone-responsive phosphatase hydrolyses lysophosphatidic acid within the plasma membrane of ovarian cancer cells.

Lysophosphatidic acid (LPA) mediates pleomorphic effects on multiple cell lineages, including an increased proliferative response of ovarian cancer cells both in vitro and in vivo, at least in part through the novel expression of LPA receptors. Thus, LPA hydrolysis is necessary to limit the duration of LPA's action on multiple cell types, including ovarian cancer cells. We determined the principal mechanism of LPA hydrolysis by ovarian cancer cells and its regulation by GnRH, which is known to have antiproliferative actions on ovarian carcinomas. LPA-hydrolyzing activity in cell membranes of ovarian cancer specimens was assessed by measuring the conversion of exogenous [3H-oleoyl]LPA to [3H]oleic acid or mono[3H-oleoyl]glycerol. Approximately 98% of LPA hydrolysis could be accounted for by the dephosphorylation of LPA to yield monoglyceride, with the deacylation reaction accounting for less than 1% of LPA hydrolysis. The phosphatase activity in the plasma membrane ovarian cancer cells was approximately 2.5- and 8-fold higher than those in microsome and homogenate fractions, respectively. The membrane phosphatase was Mg2+ independent and insensitive to inhibition by N-ethylmaleimide, characteristics suggestive of phosphatidic acid phosphatase activity. Incubation of membranes from GnRH receptor-positive ovarian cancer specimens with the GnRH agonist, buserelin, induced a dose-dependent increase in LPA phosphatase activity, with a half-maximal effect occurring with 30 nmol/L buserelin. The stimulatory action of buserelin could be neutralized by displacement of GnRH from its receptor by the GnRH antagonist, antide. The plasma membranes from GnRH receptor-negative ovarian cancer specimens did not respond to GnRH stimulation. LPA phosphatase activity was also increased when the ovarian cancer cell line Caov-3 was exposed to GnRH agonist in intact cells before assay of cell membranes. These data demonstrate that LPA is hydrolyzed in the plasma membrane of ovarian cancer cells by the action of LPA phosphatase and provide initial evidence for functional coupling of LPA phosphatase to GnRH receptor occupancy.

Adenocarcinoma, Clear Cell↗
PubMed2000

Sarcomatous transformation of a prolactinoma associated with development of a fatal internal carotid artery pseudoaneurysm--case report.

A 21-year-old female with a 5-year history of prolactinoma was referred to our hospital because of cerebrospinal fluid leakage and meningitis immediately following a third transsphenoidal operation for a rapidly growing tumor. Histological examination of the tumor removed at the second transsphenoidal operation found atypical epithelial and sarcomatous components. Administration of bromocriptine, radiotherapy, and chemotherapy were initiated. Emergent craniotomy was required for rapid regrowth of the tumor. Histological examination found predominant sarcomatous components. Tumor growth was difficult to control. The patient died of subarachnoid hemorrhage due to rupture of a pseudoaneurysm involving the C1 portion of the right internal carotid artery. Pituitary adenoma rarely shows malignant transformation. In this case, prolactinoma underwent malignant change to sarcoma. Development of the pseudoaneurysm may have resulted from surgical manipulation, radiotherapy, or tumor invasion.

Adult↗
PubMed1999

The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells.

The PTEN/MMAC1/TEP (PTEN) tumor suppressor gene at 10q23.3 is mutated in multiple types of sporadic tumors including breast cancers and also in the germline of patients with the Cowden's breast cancer predisposition syndrome. The PTEN gene encodes a multifunctional phosphatase capable of dephosphorylating the same sites in membrane phosphatidylinositols phosphorylated by phosphatidylinositol 3'-kinase (PI3K). We demonstrate herein that loss of PTEN function in breast cancer cells results in an increase in basal levels of phosphorylation of multiple components of the P13K signaling cascade as well as an increase in duration of ligand-induced signaling through the P13K cascade. These alterations are reversed by wild-type but not phosphatase inactive PTEN. In the presence of high concentrations of serum, enforced expression of PTEN induces a predominant G1 arrest consistent with the capacity of PTEN to evoke increases in the expression of the p27Kip1 cyclin dependent kinase inhibitor. In the presence of low concentrations of serum, enforced PTEN expression results in a marked increase in cellular apoptosis, a finding which is consistent with the capacity of PTEN to alter the phosphorylation, and presumably function, of the AKT, BAD, p70S6 kinase and GSK3 alpha apoptosis regulators. Under anchorage-independent conditions, PTEN also induces anoikis, a form of apoptosis that occurs when cells are dissociated from the extracellular matrix, which is enhanced in conjunction with low serum culture conditions. Together, these data suggest that PTEN effects on the PI3K signaling cascade are influenced by the cell stimulatory context, and that depending on the exposure to growth factors and other exogenous stimuli such as integrin ligation, PTEN can induce cell cycle arrest, apoptosis or anoikis in breast cancer cells.

Apoptosis↗
PubMed1999

Overexpression of edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner.

Lysophosphatidic acid (LPA) is one of the major growth factors in ascites from ovarian cancer patients and appears to play an important role in proliferation, survival, and invasion of ovarian cancer cells. Recently, several groups have shown that Edg-2, which belongs to the G-protein coupled receptor family, is a functional LPA receptor. Northern blot analysis showed that most ovarian cancer cell lines express Edg-2. Edg-2 expression was especially high in the cisplatin-resistant and slowly proliferating 2780cp cell line and was almost absent from the cisplatin-sensitive and rapidly proliferating A2780 cell line. We thus assessed whether Edg-2 could contribute to changes in cell viability, cell proliferation, or cisplatin resistance. Stable overexpression of Edg-2 in A2780 cells induced an exogenous LPA-independent decrease in proliferation but did not alter cisplatin sensitivity. The LPA-independent decrease in growth rate induced by overexpression of Edg-2 could be explained, at least in part, by Edg-2-induced apoptosis rather than by effects on cell cycle progression. In agreement with the results in stably transfected A2780 cells, transient expression of Edg-2 in Jurkat T cells also induced apoptosis. When cells were separated from the extracellular matrix, they underwent a specialized form of apoptosis called anoikis, which is particularly important in survival of cells in the circulation during metastasis. A2780 cells engineered to overexpress Edg-2 were particularly sensitive to anoikis. These observations suggest that Edg-2 may be a negative regulator for ovarian epithelial cell growth and metastasis.

Animals↗