PubMed Health⌕ Search

Biomedical subjects

A Tani

Publications and source records attributed to A Tani.

At least 55 records · Page 3Linked to original sources
PubMed1999

An enhanced active efflux of CPT-11 and SN-38 in cisplatin-resistant human KB carcinoma cells.

Cisplatin-resistant KCP-4 cells were 12.4- and 31.6-fold more resistant to CPT-11 and SN-38 than parental KB-3-1 cells, respectively. We studied the mechanism of cross-resistance to CPT-11 and SN-38. Our previous study showed that multidrug resistance protein (MRP), canalicular multispecific organic anion transporter (cMOAT) and P-glycoprotein (P-gp) were not expressed in KCP-4 cells (Chen, Z.-S. et al., Exp. Cell Res., 240 (1998) 312-320, and Chuman, Y. et al., Biochem. Biophys. Res. Commun., 226 (1996) 158-165). The accumulation of both CPT-11 and SN-38 in KCP-4 cells was lower than that in KB-3-1 cells. The ATP-dependent efflux of CPT-11 and SN-38 from KCP-4 cells was enhanced compared with that from KB-3-1 cells. DNA topoisomerase (topo) I expression, topo I activity, topo I-mediated cleavable complex, and the sensitivity to SN-38 of DNA topo I in KCP-4 were similar to those in KB-3-1 cells. Furthermore, the conversion of CPT-11 to SN-38 in the two cell lines was also similar. The transport of LTC4 in KCP-4 membrane vesicles was competitively inhibited by bis-(glutathionato)-platinum (II) (GS-Pt), CPT-11 and SN-38. These findings suggested that an unknown transporter distinct from P-gp, MRP or cMOAT is expressed in KCP-4 cells and transports CPT-11 and SN-38.

ATP-Binding Cassette Transporters↗
PubMed1999

The effect of a thymidine phosphorylase inhibitor on angiogenesis and apoptosis in tumors.

Thymidine phosphorylase (TP) is an enzyme involved in the reversible conversion of thymidine to thymine and is identical to an angiogenic factor, platelet-derived endothelial cell growth factor. TP is expressed at higher levels in a wide variety of solid tumors than in the adjacent nonneoplastic tissues. Patients with TP-positive colon and esophageal tumors have a poorer prognosis than those with TP-negative tumors. We have recently synthesized a new TP inhibitor (TPI), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride. We investigated the effect of TPI on angiogenesis in KB cells transfected with platelet-derived endothelial cell growth factor cDNA, KB/TP, and a mock transfectant, KB/CV, using the mouse dorsal air sac assay model. We found that KB/TP cells had a higher angiogenic ability than KB/CV cells and that TPI completely suppressed angiogenesis by KB/TP. Furthermore, at a dose of 50 mg/kg/day, TPI considerably decreased the growth rate of KB/TP cells xenografted into nude mice. Microvessel density in KB/TP tumors was higher than that in KB/CV tumors, and TPI did not significantly change the density in either of the tumors. The apoptotic index in KB/TP tumors was significantly lower than that in KB/CV tumors, and TPI significantly increased the apoptotic index in KB/TP tumors but not in KB/CV tumors. These findings, taken together with previous reports, suggest that the expression of TP plays an important role in tumor growth and that TPI suppresses tumor growth by increasing the proportion of apoptotic cells and probably inhibiting angiogenesis.

Animals↗
PubMed1999

17beta-estradiol induces apoptosis in the preosteoclastic FLG 29.1 cell line.

Although compelling data have demonstrated the effectiveness of estrogen replacement therapy for the treatment of accelerated bone loss in postmenopausal osteoporosis and ovariectomized animals, the mechanisms by which estrogens reduce bone resorption remain to be elucidated. To address this issue, in the present study we investigated whether estrogens were able to induce programmed cell death or apoptosis in osteoclast precursors. To this purpose, a preosteoclastic cell line (FLG 29.1) was cultured in the absence or presence of nanomolar concentrations of 17beta-estradiol (17betaE2). Using time-lapse videomicroscopy, it was shown that 17betaE2 induced FLG 29.1 cell apoptosis in a dose- and time-dependent manner. Furthermore, a significant increase in the activity of caspase 3 enzyme and in the number of nuclei undergoing DNA fragmentation was observed in FLG 29.1 cells treated with 17betaE2 compared to untreated cells. Finally, transmission electron microscopy of the treated cells showed typical apoptotic morphology. These data indicate that 17betaE2 is able to promote in vitro apoptosis in preosteoclastic cells and suggest that estrogenic molecules may exert in vivo a direct role in negatively modulating the pool of undifferentiated bone marrow cells capable ultimately of maturing into osteoclasts.

Apoptosis↗
PubMed1999

Indium-111-chloride scintigraphy visualized gastric involvement in a case of adult T-cell leukemia.

We report a case of adult T-cell leukemia (ATL) with gastric involvement visualized by 111In-chloride scintigraphy. A 55-year-old male patient presented with upper abdominal pain and appetite loss. His barium gastric series showed multiple ulcerating polypoid tumors due to gastric involvement of ATL. These lesions accumulated 111In-chloride and were also avid for 67Ga-citrate. Although the mechanism of 111In-chloride accumulation is unknown, 111In-chloride scintigraphy may be useful in evaluating patients with ATL.

Bone Marrow↗
PubMed1999

Iodine-123 iodobenzofuran (I-123 IBF) SPECT in patients with parkinsonism.

I-123 IBF is a dopaminergic antagonist which is suitable for SPECT imaging of D2 receptors. The purpose of this study is to evaluate the potential usefulness of semi-quantitative parameters obtained from brain SPECT data of I-123 IBF for differential diagnosis in patients with parkinsonism (PN). Subjects were 10 patients with PN: 2 patients with striato-nigral degeneration (SND), 5 patients with Parkinson's disease (PD), 2 patients with progressive supranuclear palsy (PSP) and one patient with olivo-ponto-cerebellar atrophy (OPCA). The data were acquired with a triple-head gamma camera at 2 hours after intravenous injection of 167 MBq of I-123 IBF. Transverse images were reconstructed by means of filtered backprojection, and attenuation correction was performed by Chang's method (mu = 0.08). The basal ganglia-to-frontal cortex ratio (GFR) and the basal ganglia-to-occipital cortex ratio(GOR) on slices of 5 different thicknesses were calculated. The GFR and GOR were lower in the SND group than in the other disease groups in all slices with different thicknesses (7.2 mm, 14.4 mm, 21.6 mm, 28.8 mm and 43.2 mm). The semiquantitative parameters (GFR and GOR) obtained from brain SPECT data at 2 hours after intravenous injection of I-123 IBF may be useful for differential diagnosis in patients with PN.

Aged↗
PubMed1999

Elective induction of labor at 39 weeks of gestation: a prospective randomized trial.

OBJECTIVE: To clarify the safety of elective induction of labor at 39 weeks of gestation. STUDY DESIGN: Prospective randomized study. SUBJECTS AND METHODS: Uncomplicated nulliparas (N = 194) were randomly assigned at 36 weeks of gestation. Labor was electively induced in 63 women at 39 weeks of gestation in the active management group (I group, N = 98). Spontaneous labor onset was expected with semi-weekly nonstress test (NST) and amniotic fluid index (AFI) by 42 weeks of gestation in the expectant group (E group, N = 96). Perinatal events were compared between the 2 groups. RESULTS: A significantly higher incidence of meconium-stained amnios (19.4% vs 3.2%) and fetal resuscitation (16.7% vs 4.8%) was found in the E group than in the I group. Also, although a significantly higher incidence of epidural analgesia was noted in the I group (89%) than in the E group (54%) (labor onset > or = 39 weeks, N = 72), the duration of the 1st stage was shorter in I group and the duration of the 2nd stage was not significantly different. No other significant difference was noted between the 2 groups in terms of the rate of C-section, blood loss, incidence of pathological FHR, birth weight, Apgar score, umbilical arterial pH, or admission to NICU. CONCLUSION: Active management of labor at 39 weeks could be made as safely as expectant management with modified biophysical profile monitoring.

Adult↗
PubMed1999

Impaired diurnal cardiac autonomic function in subjects with type 2 diabetes.

OBJECTIVE: To assess diurnal cardiac sympathetic and parasympathetic nerve functions in diabetic subjects with variable diabetic neuropathy. RESEARCH DESIGN AND METHODS: Frequency domain analysis of 24-h Holter ECG was done for 132 diabetic subjects (84 without any symptomatic neuropathy; 37 with only symptomatic peripheral neuropathy; 11 with symptomatic autonomic neuropathy) and 57 normal volunteers to calculate the low frequency (LF) component representing the beta-adrenoceptor function and the high frequency (HF) component representing the cardiac parasympathetic nerve function. RESULTS: Cardiac LF and HF components in diabetic subjects without peripheral neuropathy showed values comparable to those of normal volunteers and a similar circadian rhythm. Diabetic subjects with peripheral neuropathy or autonomic neuropathy showed significantly depressed LF and HF components and loss of the circadian rhythm of LF and HF components compared with diabetic subjects without neuropathy. Impairment of the LF component in the afternoon could be accounted for by the duration of diabetes and elevated HbA1c level. Impairment of the HF component at night could be accounted for by the duration of diabetes but not an elevated HbA1c level. CONCLUSIONS: These data indicated that diabetic subjects with peripheral neuropathy and diabetic subjects with symptomatic autonomic neuropathy, but not diabetic subjects without neuropathy, showed a marked decrease in cardiac sympathetic and parasympathetic nerve functions and loss of circadian rhythm.

Adult↗
PubMed1998

Prevention of hypoxia-induced apoptosis by the angiogenic factor thymidine phosphorylase.

The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is expressed at higher levels in a wide variety of solid tumors compared to adjacent normal tissues. Patients with PD-ECGF/TP-positive colon and esophageal tumors have a poorer prognosis than those with negative tumors. The expression of PD-ECGF/TP is a prognostic factor independent of microvessel density suggesting that TP has effects on tumor progression independent of its angiogenic activity. Evidence that hypoxia and apoptosis affect tumor growth prompted us to determine whether increased expression of PD-ECGF/TP prevents apoptosis induced by hypoxia. KB/TP cells transfected with a PD-ECGF/TP cDNA were resistant to hypoxia-induced apoptosis. Among the degradation products of thymidine produced by PD-ECGF/TP, 2-deoxy-D-ribose and thymine partially prevented hypoxia-induced apoptosis. The ability of 1 microM 2-deoxy-D-ribose in combination with the same concentration of thymine to prevent hypoxia-induced apoptosis was similar to that of the overexpressed TP in KB cells. A concentration of 1 microM 2-deoxy-L-ribose abrogated the effects of these degradation products of thymidine. These findings suggested that TP can confer resistance to apoptosis induced by hypoxia and the degradation products of thymidine are involved in this resistance. Expression of PD-ECGF/TP may play an important role in the progression of solid tumors, and inhibitors of TP and analogs of the degradation products of thymidine may suppress the growth of tumors by promoting apoptosis.

Angiogenesis Inducing Agents↗
PubMed1998

Increased sensitivity to vincristine of MDR cells by the leukotriene D4 receptor antagonist, ONO-1078.

The leukotriene D4 (LTD4) receptor antagonist, 4-oxo-8-[p-(4-phenylbutyloxy)benzoylamino]-2-(tetrazol-5-yl) -4H-1-benzopyran hemihydrate (ONO-1078) is used for the treatment of allergic asthma and other immediate hypersensitivity diseases. We examined the effect of ONO-1078 on the sensitivity to vincristine (VCR) of MRP overexpressing multidrug-resistant CV60 and its parental drug-sensitive KB-3-1 cell lines. The sensitivity to VCR of KB-3-1 and CV60 cells was increased 13- and 15-fold, respectively, by ONO-1078 at the maximum non-toxic concentration (100 microM). The VCR sensitivity of multidrug-resistant KB-C2 cells that overexpressed P-gp was increased 2.6-fold by ONO-1078. The accumulation of VCR in KB-3-1, CV60 and KB-C2 cells was significantly increased by ONO-1078. The efflux of VCR from KB-3-1 cells was not inhibited, but that from CV60 cells was enhanced compared with that from KB-3-1 cells and was partially inhibited by ONO-1078. ONO-1078 competitively inhibited the ATP-dependent [3H]LTC4 uptake in membrane vesicles isolated from CV60 cells. These findings suggest that ONO-1078 inhibits the transporting activity of MRP and that ONO-1078 increases the sensitivity to VCR of KB-3-1 cells by increasing the VCR uptake in the cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Reversal of MRP-mediated vincristine resistance in KB cells by buthionine sulfoximine in combination with PAK-104P.

The mechanism of multidrug resistance protein (MRP)-mediated multidrug resistance (MDR) is still unclear. MRP reportedly transports some GSH conjugates. Recently, we demonstrated that a pyridine analog, 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl 5-(trans-4,6-dimethyl-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4 -(3-nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P), that reversed P-glycoprotein (P-gp)-mediated MDR directly interacted with MRP and completely reversed the vincristine (VCR) resistance in MRP-mediated MDR C-A120 cells. We investigated the reversing effect of PAK-104P in C-A120 cells in combination with buthionine sulfoximine (BSO), another MDR-reversing agent with a different reversing mechanism. In immunoblots, MRP was overexpressed in C-A120 cells. The level of ATP-dependent [3H]VCR uptake was high in membrane vesicles from KB-C2 cells, but low in those from C-A120 and parental KB-3-1 cells. The sensitivity to VCR of C-A120 cells, but not of KB-C2 cells, was considerably increased by 100 microM BSO. VCR accumulation in C-A120 cells, but not in KB-C2 cells, was also enhanced by BSO. BSO did not inhibit ATP-dependent [3H]LTC4 uptake in C-A120 vesicles. The combination of BSO with PAK-104P at their low concentrations resulted in complete reversal of VCR resistance in C-A120 cells. These findings suggested that BSO might not directly interact with MRP and reversed resistance in MRP-mediated MDR cells by reducing the intracellular glutathione (GSH) level that was needed for the transport of drugs by MRP and suggested a role for the combination of drug resistance-modulating agents with different reversing mechanisms in the reversal of MRP-mediated MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

An active efflux system for heavy metals in cisplatin-resistant human KB carcinoma cells.

The mechanism for cisplatin resistance in cisplatin-resistant KCP-4 cells was studied. Although multidrug resistance-associated protein (MRP) was not detected in KCP-4 cells, the cells were more resistant to heavy metals than multidrug-resistant C-A120 cells that overexpressed MRP. KCP-4 cells expressed metallothionein, but it was scarcely involved in cisplatin resistance in these cells. KCP-4 cells did not express canalicular multispecific organic anion transporter (cMOAT). The glutathione (GSH) level was 4.7-fold higher in KCP-4 cells than in KB-3-1 cells. When the GSH level in KCP-4 cells was decreased by treating the cells with buthionine sulfoximine and nitrofurantoin, the accumulation of and sensitivity to cisplatin in the cells were increased. C-A120 cells were only 3.0-fold more resistant to cisplatin than KB-3-1 cells and this resistance was not affected by the increased glutathione level. The accumulation of platinum in C-A120 and KCP-4 cells was 68.5 and 20.4% of that in KB-3-1 cells, respectively, while the intracellular levels of antimony potassium tartrate in C-A120 and KCP-4 cells were 13.2 and 9.9% of that in KB-3-1 cells, respectively. The ATP-dependent efflux of antimony was enhanced in both C-A120 and KCP-4 cells. These results, taken together, suggest an efflux pump for heavy metals different from MRP and cMOAT is involved in cisplatin resistance in KCP-4 cells.

ATP-Binding Cassette Transporters↗
PubMed1998

The expression of multidrug resistance protein in human gastrointestinal tract carcinomas.

BACKGROUND: Multidrug resistance protein (MRP) is a membrane phosphoglycoprotein with an Mr of 190,000 that is involved in the non-P-glycoprotein mediated multidrug resistance of human tumor cells. The aim of this study was to determine the clinicopathologic relevance of MRP expression in human gastrointestinal tract carcinomas. METHODS: The authors prepared a rabbit antiserum against MRP that does not cross-react with P-glycoprotein and retrospectively examined the expression of MRP in 86 squamous cell carcinomas of the esophagus, 103 adenocarcinomas of the stomach, and 139 colorectal adenocarcinomas by immunohistochemistry. None of the patients in this study had received prior chemotherapy. RESULTS: The proportion of MRP positive samples in the squamous cell carcinomas of the esophagus (62.8%, 54 of 86) was significantly higher than that in the adenocarcinomas of the stomach (34.1%, 35 of 103) and the colorectal adenocarcinomas (40.3%, 56 of 139) (P <0.01). The proportion of MRP positivity in the well-differentiated carcinomas was significantly higher than that in moderately or poorly differentiated carcinomas. MRP expression was independent of gender, lymph node metastasis, and tumor progression. CONCLUSIONS: These data indicate that the expression of MRP is correlated with the differentiation of carcinoma cells in the gastrointestinal tract and may be involved in the intrinsic drug resistance of well-differentiated squamous cell carcinoma of the esophagus.

ATP-Binding Cassette Transporters↗
PubMed1998

Persistent damage to Enterocytozoon bieneusi, with persistent symptomatic relief, after combined furazolidone and albendazole in AIDS patients.

AIM: To investigate morphological changes in Enterocytozoon bieneusi and the duration of symptomatic relief after combination treatment with furazolidone and albendazole in AIDS patients. METHODS: Four severely immunocompromised AIDS patients with symptomatic E bieneusi infection of the gut received an 18 day course of combined furazolidone and albendazole (500 + 800 mg daily). All patients were monitored for parasite shedding in stool by light microscopy at the end of treatment and monthly during follow up. At the end of treatment, duodenal biopsy specimens obtained from three patients were studied by transmission electron microscopy by two pathologists blind to the patients' treatment or clinical outcome. Duodenal biopsy specimens obtained from one of the patients two months after completion of treatment were also studied electronmicroscopically. RESULTS: All patients had long lasting symptomatic relief, with a major decrease--or transient absence--of spore shedding in stools from completion of treatment. After treatment, changes in faecal spores were persistently found by light microscopy in all cases, and there was evidence of both a substantial decrease in the parasite load and ultrastructural damage in the parasite in all biopsy specimens. The treatment was well tolerated, and no patient had clinical or parasitological relapse during follow up (up to 15 months). CONCLUSIONS: The long lasting symptomatic relief observed in all four treated patients correlated with the persistent decrease in parasite load both in tissue and in stool, and with the morphological changes observed in the life cycle of the protozoan. These data suggest that combined treatment with furazolidone and albendazole is active against E bieneusi and may result in lasting remission even in severely immunocompromised patients.

AIDS-Related Opportunistic Infections↗