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Biomedical subjects

H Ishihara

Publications and source records attributed to H Ishihara.

At least 235 records · Page 13Linked to original sources
PubMed1996

Cloning of cDNAs encoding two isoforms of 68-kDa type I phosphatidylinositol-4-phosphate 5-kinase.

Accumulating evidence suggests that phosphatidylinositol metabolism is essential for membrane traffic in the cell. Of particular importance, phosphatidylinositol transfer protein and the type I phosphatidylinositol- 4-phosphate 5-kinase (PI4P5K) have been identified as cytosolic components required for ATP-dependent, Ca2+-activated secretion. In order to identify PI4P5K isoforms that may play important roles in regulated insulin secretion from pancreatic beta-cells, we employed the polymerase chain reaction with degenerate primers and screening of a cDNA library of the murine pancreatic beta-cell line MIN6. Two novel cDNAs, designated PI4P5K-Ialpha and PI4P5K-Ibeta, were identified, which contained complete coding sequences encoding 539- or 546-amino acid proteins, respectively. These cDNAs were expressed in mammalian cells with an adenoviral expression vector. Proteins of both isoforms migrated at 68 kDa on SDS-polyacrylamide gel electrophoresis and exhibited phosphatidylinositol-4-phosphate 5-kinase activity, which was activated by phosphatidic acid, indicating that these proteins were type I isoforms. While these isoforms share a marked amino acid sequence homology in their central portion, the amino- and carboxyl-terminal regions differ significantly. Northern blot analysis depicted that tissue distributions differed between the two isoforms. Molecular identification of type I PI4P5K isoforms in insulin-secreting cells should provide insights into the role of phosphatidylinositol metabolism in regulated exocytosis of insulin-containing large dense core vesicles.

Amino Acid Sequence↗
PubMed1996

Overexpression of either liver type or pancreatic beta cell type glucokinase via recombinant adenovirus enhances glucose oxidation in isolated rat hepatocytes.

To elucidate a role of glucokinase in hepatic glucose metabolism, we overexpressed hexokinase I (HKI), liver type glucokinase (LGK), or beta cell type glucokinase (beta GK) in primary rat hepatocytes using a recombinant adenovirus vector system. Overexpression of HKI and LGK induced a 34- and 25-fold increase, respectively, in glucose phosphorylation activity measured in cell homogenates. While HKI overexpression induced only a 1.3-fold increase in glucose oxidation, LGK overexpression increased glucose oxidation by 2.9-fold. Overexpression of beta GK had essentially the same effect as LGK. The results indicate that glucokinase does indeed regulate the rate of hepatic glucose oxidation and that the liver-specific sequence of this enzyme is not essential for this function.

Adenoviruses, Human↗
PubMed1996

Functional importance of amino-terminal domain of Shc for interaction with insulin and epidermal growth factor receptors in phosphorylation-independent manner.

Shc has two distinct domains, amino-terminal and SH2 domain, which can interact with activated growth factor receptors. Shc interacts with insulin receptor via Shc-amino-terminal (N) domain, whereas Shc associates with epidermal growth factor (EGF) receptor through both Shc-N and -SH2 domains. In accordance with the different functional roles between insulin and EGF receptors, EGF stimulated tyrosine phosphorylation of Shc faster than insulin. To clarify the functional importance of three distinct Shc domains on insulin and EGF signaling, we microinjected glutathione S-transferase (GST) fusion proteins containing the amino terminus plus collagen homology domain (NCH), collagen homology domain (CH), and Src homology 2 domain (SH2) into Rat1 fibroblasts expressing insulin receptors (HIRc). Bromodeoxyuridine (BrdUrd) incorporation into newly synthesized DNA was subsequently studied to assess the importance of the three distinct domains of Shc. Microinjection of the NCH-GST fusion protein inhibited BrdUrd incorporation induced by both EGF and insulin, whereas microinjection of the SH2-GST fusion protein inhibited EGF, but not insulin stimulation of DNA synthesis. Neither EGF- nor insulin-induced BrdUrd incorporation was inhibited by the CH-GST fusion protein. Following EGF or insulin stimulation, Shc is phosphorylated on single Tyr-317 residue serving as a docking site for Grb2. Microinjection of Shc-N+CH GST fusion protein with Tyr-317 --> Phe replacement (Y317F) also inhibited insulin stimulation of DNA synthesis. Next, we stably overexpressed wild-type Shc or Y317F mutant Shc into HIRc cells. Insulin-induced tyrosine phosphorylation of IRS-1 was compared among the transfected cell lines, since IRS-1 and Shc could competitively interact with insulin receptor. Insulin-stimulated tyrosine phosphorylation of IRS-1 was decreased in both WT-Shc and Y317F-Shc cells compared with that in HIRc cells. Furthermore, overexpression of the Shc-SH2 domain or Shc-N+CH domain with Y317F mutation interfered with EGF-stimulated endogenous Shc phosphorylation. These results suggest that the amino terminus domain of Shc is functionally important in insulin- and EGF-induced cell cycle progression and that the phosphorylation of Shc Tyr-317 residue is independent of Shc interaction with these receptors.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Overexpression of catalytic subunit p110alpha of phosphatidylinositol 3-kinase increases glucose transport activity with translocation of glucose transporters in 3T3-L1 adipocytes.

To elucidate the mechanisms of phosphatidylinositol (PI) 3-kinase involvement in insulin-stimulated glucose transport activity, the epitope-tagged p110alpha subunit of PI 3-kinase was overexpressed in 3T3-L1 adipocytes using an adenovirus-mediated gene transduction system. Overexpression of p110alpha was confirmed by immunoblot using anti-tagged epitope antibody. p110alpha overexpression induced a 2.5-fold increase in PI 3-kinase activity associated with its regulatory subunits in the basal state, an increase exceeding that of the maximally insulin-stimulated control cells, while PI 3-kinase activity associated with phosphotyrosyl protein was only modestly elevated. Overexpression of p110alpha induced an approximately 14-fold increase in the basal glucose transport rate, which was also greater than that observed in the stimulated control. No apparent difference was observed in the cellular expression level of either GLUT1 or GLUT4 proteins between control and p110alpha-overexpressing 3T3-L1 adipocytes. Subcellular fractionation revealed translocation of glucose transporters from intracellular to plasma membranes in basal p110alpha-overexpressing cells. The translocation of GLUT4 protein to the plasma membrane was further confirmed using a membrane sheet assay. These findings indicate that an increment in PI 3-kinase activity induced by overexpression of p110alpha of PI 3-kinase stimulates glucose transport activity with translocation of glucose transporters, i.e., mimics the effect of insulin.

3T3 Cells↗
PubMed1996

Effect of glimepiride (HOE 490) on insulin receptors of skeletal muscles from genetically diabetic KK-Ay mouse.

A new sulfonylurea, glimepiride (HOE 490), has been developed for the glycemic control in non-insulin-dependent diabetes mellitus. We examined the effect of glimepiride on glucose and insulin levels in KK-Ay mice, an animal model of non-insulin-dependent diabetes mellitus, which is characterized by hyperglycemia and hyperinsulinemia. Administration of glimepiride (0.5 mg/kg/day) for 8 weeks to KK-Ay mice resulted in decrease in glucose (297 +/- 36 to 250 +/- 51 mg/dl) and insulin (76 +/- 14 to 41 +/- 14 microU/ml) levels. To clarify the mechanism of the agent, we examined the effect of this new drug on insulin receptors in the skeletal muscles. There was no difference in insulin binding to the receptors from both glimepiride-treated and -untreated KK-Ay mice muscles. The insulin-stimulated autophosphorylation of insulin receptors from KK-Ay mice was decreased compared to that from normal mice (5 +/- 1 vs. 39 +/- 13% over basal). Glimepiride did not ameliorate impaired insulin-stimulated insulin receptor autophosphorylation. To determine the effect of glimepiride on post-insulin receptor signaling pathway, we measured 2-[3H]glycerol incorporation into diacylglycerol in the cultured rat fibroblast cell line overexpressing human insulin receptors. Glimepiride (100 microM) as well as insulin (10 nM) significantly stimulated diacylglycerol production. These results suggest that glimepiride has a potent extrapancreatic effect on glucose metabolism and may directly stimulate glucose transport activity through phospholipid signaling pathway, but not through insulin receptor kinase signaling pathway.

Animals↗
PubMed1996

Molecular cloning of human mitochondrial glycerophosphate dehydrogenase gene: genomic structure, chromosomal localization, and existence of a pseudogene.

cDNA of mitochondrial glycerophosphate dehydrogenase (mGPDH), a defect of which is a possible cause of non-insulin dependent diabetes mellitus, was cloned from a human insulinoma cDNA library. The deduced amino acid sequence showed 91% and 92% homology with those of rat and mouse mGPDH, respectively. The mGPDH gene was mapped to chromosome 2q23 by FISH analysis. Genomic clones for mGPDH were then isolated using mouse mGPDH cDNA and PCR products of human mGPDH cDNA as probes. Genomic structure was studied by sequencing the exon-intron boundaries and by PCR amplification of intronic regions using genomic clones as templates. The human mGPDH gene was shown to be composed of 15 coding exons, containing a (CA)n repeat region inside the gene, which was not polymorphic in the Japanese population. Genomic cloning also identified a pseudogene located on chromosome 19q13.4. These results provide information useful for analyzing the mGPDH gene in patients with non-insulin dependent diabetes mellitus.

Amino Acid Sequence↗
PubMed1996

Contribution of proline residues in the membrane-spanning domains of cystic fibrosis transmembrane conductance regulator to chloride channel function.

Proline residues located in membrane-spanning domains of transport proteins are thought to play an important structural role. In the cystic fibrosis transmembrane conductance regulator (CFTR), the predicted transmembrane segments contain four prolines: Pro99, Pro205, Pro324, and Pro1021. These residues are conserved across species, and mutations of two (P99L and P205S) are associated with cystic fibrosis. To evaluate the contribution of these prolines to CFTR Cl- channel function, we mutated each residue individually to either alanine or glycine or mutated all four simultaneously to alanine (P-Quad-A). We also constructed the two cystic fibrosis-associated mutations. cAMP agonists stimulated whole cell Cl- currents in HeLa cells expressing the individual constructs that resembled those produced by wild-type CFTR. However, the amount of current was decreased in the rank order: wild-type CFTR = Pro324 > Pro1021 > Pro99 >/= Pro205 mutants. The anion selectivity sequence of the mutants (Br- >/= Cl- > I-) resembled wild-type except for P99L (Br- >/= Cl- = I-). Although the Pro99, Pro324, and Pro1021 mutants produced mature protein, the amount of mature protein was much reduced with the Pro205 mutants, and the P-Quad-A made none. Because the Pro99 constructs produced mature protein but had altered whole cell currents, we investigated their single-channel properties. Mutant channels were regulated like wild-type CFTR; however, single-channel conductance was decreased in the rank order: wild-type CFTR >/= P99G > P99L >/= P99A. These results suggest that proline residues in the transmembrane segments are important for CFTR function, Pro205 is critical for correct protein processing, and Pro99 may contribute either directly or indirectly to the Cl- channel pore.

Adenosine Triphosphate↗
PubMed1996

Role of the thrombin receptor in development and evidence for a second receptor.

Thrombin, a coagulation protease generated at sites of vascular injury, activates platelets, endothelial cells, leukocytes and mesenchymal cells. A G-protein-coupled receptor that is proteolytically activated by thrombin is a target for drug development aimed at blocking thrombosis, inflammation and proliferation. Here we show that although disruption of the thrombin receptor (tr) gene in mice causes about half of the tr-/- embryos to die at embryonic day 9-10, half survive to become grossly normal adult mice with no bleeding diathesis. Strikingly, tr-/- platelets respond strongly to thrombin, whereas tr-/- fibroblasts lose their ability to respond to thrombin. We conclude that the thrombin receptor plays an unexpected role in embryonic development, suggesting a possible new function for the 'coagulation' proteases themselves. Moreover, a second platelet thrombin receptor exists, and different thrombin receptors have tissue-specific roles. This may allow development of therapeutics that will selectively block thrombin's different cellular actions.

Adenosine Triphosphate↗
PubMed1996

Hsp70 family molecular chaperones and mutant insulin receptor: differential binding specificities of BiP and Hsp70/Hsc70 determines accumulation or degradation of insulin receptor.

We have examined the binding specificities of Hsp70 family molecular chaperones, BiP and Hsp70/Hsc70, to wild-type or mutant insulin receptors. BiP bound to proreceptor of wild-type insulin receptor, but not to mature receptor. A mutant insulin receptor, which lacked 47 amino acid residues (delta Ex13 IR) corresponding to exon 13 of insulin receptor gene, accumulated in the endoplasmic reticulum as uncleaved proreceptor with immature oligosaccharide chains. This deletion mutant bound to BiP more tightly than wild type. Introduction of two types of mutations, Asp1179 or Leu1193, into delta Ex13 IR led to accelerated degradation, and these double mutants bound weakly to BiP. In contrast, Ser735 insulin receptor was normally transported to the plasma membrane and normally bound to BiP. Furthermore, Asp1179, Leu1193 insulin receptors and delta Ex13 IR combination mutant with either Asp1179 or Leu1193 bound more tightly to Hsp70/Hsc70 compared with wild-type, Ser735, and delta Ex13 IR. These results suggest that the binding specificity of mutant insulin receptors to two molecular chaperones, i.e., BiP and Hsp70/Hsc70, plays an important role for their posttranslational processing that may lead to the accumulation in the endoplasmic reticulum or the degradation of insulin receptors.

Animals↗
PubMed1996

Correlation between left ventricular contractility and relaxation in patients with idiopathic dilated cardiomyopathy.

BACKGROUND AND HYPOTHESIS: It is not fully understood whether alterations in left ventricular (LV) relaxation in patients with idiopathic dilated cardiomyopathy (DCM) precede or follow alterations in LV systolic function. Accordingly, we investigated the relationship between LV systole and diastolic relaxation in patients with DCM using LV pressure-volume analysis. METHODS: Hemodynamic data were collected for 38 consecutive patients with DCM in normal sinus rhythm and in the resting steady state (New York Heart Association functional class II to III). Continuous simultaneous pressure-volume relationships were obtained by conductance catheter. Left ventricular end-systolic elastance (Ees) was determined during transient occlusion of the inferior vena cava. RESULTS: Left ventricular ejection fraction, peak negative dP/dt, and peak positive dP/dt were depressed (31 +/- 11%, -1242 +/- 351 mmHg/s, and 1118 +/- 253 mmHg/s, respectively). The LV end-diastolic volume index, the time constants of isovolumic LV pressure decay TL and TD were increased (141 +/- 38 ml/m2, 54 +/- 14 ms, and 69 +/- 17 ms, respectively). Ees was markedly depressed (0.9 +/- 0.5 mmHg/ml) and was not correlated with established systolic or diastolic indices except for peak positive dP/dt. Our results showed that abnormalities of relaxation were not correlated with contractile dysfunction in patients with DCM in the resting steady state; however, most patients (79%) had both prolonged relaxation and extremely depressed contractility. Abnormal relaxation may have been transient or compensated in some patients (21%) with DCM who had preserved relaxation despite severely depressed contractility.

Adolescent↗
PubMed1996

Autocrine/paracrine mechanism of insulin-like growth factor-1 secretion, and the effect of insulin-like growth factor-1 on proteoglycan synthesis in bovine intervertebral discs.

The present study was undertaken to investigate the effect of insulin-like growth factor-1 on proteoglycan synthesis and the autocrine/paracrine mechanism involving insulin-like growth factor-1 in the bovine coccygeal intervertebral disc. Insulin-like growth factor-1 stimulated proteoglycan synthesis in cultured cells of the nucleus pulposus of bovine intervertebral discs in a dose-dependent manner, and the effect was inhibited by an anti-insulin-like growth factor-1 monoclonal antibody. In situ hybridization histochemistry revealed the expression of insulin-like growth factor-1 mRNA in the cultured cells, and its production in these cells was demonstrated by radioimmunoassay. Insulin-like growth factor-1 receptor in the cultured cells was also demonstrated immunohistochemically. Scatchard analysis using an [125I]insulin-like growth factor-1 binding assay showed that the cells cultured in monolayer had a single type of insulin-like growth factor-1 receptor, whose affinity and number were estimated to be 7.38 x 10(8)/M and 9.27 x 10(4)/cell, respectively. These results suggest that insulin-like growth factor-1 stimulates proteoglycan synthesis in cells of the nucleus pulposus and that these cells in culture have an insulin-like growth factor-1 autocrine/paracrine mechanism. The expressions of insulin-like growth factor-1 mRNA and insulin-like growth factor-1 receptor in disc tissue were greater in cells of the nucleus pulposus of fetal bovine intervertebral discs than in those of the adult discs. These findings suggest that the action of autocrine/paracrine insulin-like growth factor-1 is more active in cells of the young nucleus pulposus than in cells of mature subjects.

Age Factors↗
PubMed1996

Cortisol and catecholamine kinetics during continuous hemodiafiltration in patients with multiple organ dysfunction syndrome.

OBJECTIVE: To assess the influence of continuous hemodiafiltration (CHDF) on cortisol and catecholamine kinetics in multiple organ dysfunction syndrome. DESIGN: Consecutive clinical study. SETTING: General intensive care unit of a university hospital. PATIENTS: Ten adult patients with multiple organ dysfunction syndrome requiring CHDF. MEASUREMENTS AND RESULTS: A total of 40 samples were collected during CHDF for cortisol and catecholamine assays. The clearances for cortisol, epinephrine, norepinephrine and dopamine were 2.5 +/- 1.7 ml/min, 26.3 +/- 2.7 ml/min, 16.7 +/- 4.2 ml/min and 26.3 +/- 2.6 ml/min (Mean +/_ SE), and their daily extractions were 1.8 +/- 0.2 mg/day, 11.4 +/- 4.8 micrograms/day, 1.0 +/- 0.1 micrograms and 2.3 +/- 0.3 micrograms/day, respectively. There were no significant changes in blood cortisol and catecholamine levels during CHDF conducted for 48 h. CONCLUSIONS: The cortisol and catecholamine losses during CHDF were small and unlikely to lead to hemodynamic disturbances.

Blood Glucose↗
PubMed1996

A novel inotropic vasodilator, OPC-18790, reduces myocardial oxygen consumption and improves mechanical efficiency with congestive heart failure.

We analyzed the left ventricular (LV) pressure-volume relation and obtained direct measurements of myocardial oxygen consumption (MVO2) before and after drug administration in 21 patients with New York Heart Association functional class II to III congestive heart failure to compare the mechanoenergetic effects of OPC-18790, a novel inotropic agent, and dobutamine. Pressure-volume data were obtained by the conductance method, and MVO2 measurements were obtained with a double-thermistor coronary sinus catheter before and after administration of OPC-18790 and dobutamine. The LV end-diastolic volume index decreased significantly without an increase in the heart rate after administration of OPC-18790, unlike that after administration of dobutamine. Both drugs significantly increased the LV contractility index (Emax) and caused similar improvements in ventricular-arterial coupling. OPC-18790 significantly reduced MVo2, whereas dobutamine increased MVo2. The ratio of the pressure-volume area to myocardial oxygen consumption (PVA/MVo2) remained unchanged after administration of OPC-18790 and decreased after administration of dobutamine. The ratio of external work to the pressure-volume area (EW/PVA) was similarly increased by both drugs, resulting in an improvement in mechanical efficiency (EW/MVo2) with OPC-18790 (p < 0.05) and in a deterioration with dobutamine (p < 0.05). OPC-18790 had an energetic advantage over dobutamine in spite of its positive inotropic effect. Our findings suggest that OPC-18790 may be useful for the treatment of patients with congestive heart failure.

Cardiotonic Agents↗
PubMed1996

The dominant negative effect of a kinase-defective insulin receptor on insulin-like growth factor-I-stimulated signaling in Rat-1 fibroblasts.

To study the interaction between insulin receptor (IR) and insulin-like growth factor-I (IGF-I) receptor (IGF-IR) tyrosine kinases, we examined IGF-I action in Rat-1 cells expressing a naturally occurring tyrosine kinase-deficient mutant IR (Asp 1048 IR). IGF-I normally stimulated receptor autophosphorylation, IRS-I phosphorylation, and glycogen synthesis in cells expressing Asp 1048 IR. However, the Asp 1048 IR inhibited IGF-I-stimulated thymidine uptake by 45% to 52% and amino acid uptake (aminoisobutyric acid [AIB]) by 58% in Asp 1048 IR cells. Furthermore, IGF-I-stimulated tyrosine kinase activity toward synthetic polymers, Shc phosphorylation, and mitogen-activated protein (MAP) kinase activity was inhibited. The inhibition of mitogenesis and AIB uptake was restored with the amelioration of the impaired tyrosine kinase activity and Shc phosphorylation by the introduction of abundant wild-type IGF-IR in Asp 1048 IR cells. These results suggest that the Asp 1048 IR causes a dominant negative effect on IGF-IR in transmitting signals to Shc and MAP kinase activation, which leads to decreased IGF-I-stimulated DNA synthesis, and that the kinase-defective insulin receptor does not affect IGF-I-stimulated IRS-I phosphorylation, which leads to the normal IGF-I-stimulated glycogen synthesis.

Animals↗
PubMed1996

In vivo direct measurement of the bronchodilating effect of sevoflurane using a superfine fiberoptic bronchoscope: comparison with enflurane and halothane.

OBJECTIVES: Although volatile anesthetics have been shown to have spasmolytic effects on constricted airways, most previous studies were performed to assess bronchodilation with indirect methods such as measurement of airway resistance, whose reliability is controversial. As the authors have developed a new direct method using a superfine fiberoptic bronchoscope (SFB) and confirmed the accuracy of this method, this study assessed the spasmolytic effect of sevoflurane (S) as compared with enflurane (E) and halothane (H). DESIGN: Open-labeled, randomized study. SETTING: The study protocol was approved by the Animal Care Committee in a school of medicine. PARTICIPANTS: Twenty-two mongrel dogs. INTERVENTIONS: The dogs were anesthetized with pentobarbital, IV, paralyzed with pancuronium, and the lungs were mechanically ventilated. The endotracheal tube had an additional lumen to insert the SFB (outer diameter 2.2 mm). The tip of the SFB was located between a second and third bronchial bifurcation to continuously monitor the bronchial cross-sectional area (BCA) of third or fourth generation bronchi. The BCA was printed out by videoprinter at the end of expiration and was calculated on a Macintosh IIci computer using an NIH (National Institutes of Health) image program. Bronchoconstriction was produced with histamine (HA: 10 micrograms/kg + 500 micrograms/kg/hr). In the first protocol, 4 mongrel dogs were used to assess the accuracy of the new method. BCA was measured 30 and 60 minutes after the placement of the SFB and also 30 and 60 minutes after the start of the histamine (HA) infusion. Arterial blood (4 mL) was collected at 30 and 60 minutes after placement of the SFB to measure the plasma concentration of catecholamines with gas chromatographic mass spectrometry. In the second protocol, 18 dogs were randomly allocated to 3 groups of 6 each: group S, group E, and group H. Thirty minutes after the start of the HA infusion, the dogs subsequently inhaled the following concentrations of S, E, or H for 15 minutes: 0.2, 0.4, 0.8, and 1.6 minimum alveolar concentrations. The BCA was assessed before and 30 minutes after the start of HA and at the end of the inhalation period of each concentration. MEASUREMENTS AND MAIN RESULTS: In the first study, no significant differences in the BCA were found between 30 and 60 minutes after the placement of the SFB and between 30 and 60 minutes after the start of HA. The plasma concentrations of norepinephrine and epinephrine changed from 138 +/- 45 and 162 +/- 18 to 188 +/- 48 and 136 +/- 18 pg/mL, respectively. In the second study, all volatile anesthetics significantly increased the BCA in a dose-dependent manner. There was no significant difference among the three groups. CONCLUSION: As the BCA did not change in the first study, the tip of the SBF could be well fixed, and the 30-minute interval is long enough for the HA infusion to produce stable bronchoconstriction. The plasma catecholamine concentrations suggest that the pentobarbital anesthesia was deep enough to inhibit the direct irritant effect of the endotracheal tube and the SFB on the airway. This new direct method indicates that S dilates HA-constricted proximal airway with the same potency as E and H.

Anesthetics, Inhalation↗
PubMed1996

The role of neoadjuvant intraarterial infusion chemotherapy with cisplatin and bleomycin for locally advanced cervical cancer.

To clarify the effect of neoadjuvant intraarterial infusion chemotherapy on the cure rate in advanced cervical cancer with bulky tumor, a total of 50 patients were examined prospectively. The clinical stage according to the International Federation of Gynecology and Obstetrics (FIGO) classification included 23 IIb, 6 IIIa, and 21 IIIb. These patients were randomly divided into the neoadjuvant intraarterial infusion chemotherapy group and the control group. There were no significant differences in mean age, FIGO clinical stage, and tumor histology between groups. Twenty-five patients in the former group were given 25 mg/m2 of cisplatin and 15 mg/m2 of bleomycin via each internal iliac artery. If the results of the evaluation indicated that surgery was feasible, radical surgery was performed. The patients whose tumors were inoperable received radiation therapy consisting of external irradiation and intracavitary irradiation. Twenty-five patients in the control group also underwent the same radiation therapy. The overall response rate was 80.0%. Eighteen of 20 responders underwent surgery. The 3-year survival rate was 85.7% for operated patients, 42.9% for patients receiving neoadjuvant intraarterial infusion chemotherapy followed by irradiation, and 49.5% for the control group. In the present study, neoadjuvant intraarterial infusion chemotherapy did not improve the prognosis of patients with advanced cervical cancer compared to radiation therapy alone, and only responders who underwent surgery obtained an advantage in survival.

Adult↗