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S Morita

Publications and source records attributed to S Morita.

At least 19 recordsLinked to original sources
PubMed2026

Eribulin versus taxane as first-line chemotherapy combined with dual HER2 blockade in patients with HER2-positive locally advanced or metastatic breast cancer: final survival outcomes of the JBCRG-M06/EMERALD study.

BACKGROUND: The phase III JBCRG-M06/EMERALD study was the first to show noninferior progression-free survival (PFS) of eribulin to taxane, combined with dual human epidermal growth factor receptor 2 (HER2) blockade (trastuzumab plus pertuzumab), as a first-line treatment for HER2-positive locally advanced breast cancer or metastatic breast cancer (LABC/MBC). We report final survival outcomes and biomarker analyses of the EMERALD trial. PATIENTS AND METHODS: Patients with HER2-positive LABC/MBC were randomly assigned 1:1 to either eribulin or physician-choice taxane (docetaxel or paclitaxel), both combined with trastuzumab plus pertuzumab, as first-line chemotherapy. PFS and overall survival (OS) were assessed through 30 June 2023 for PFS and 31 December 2024 for OS. Survival outcomes were compared between the eribulin and taxane groups and according to circulating tumor DNA (ctDNA) detection of PIK3CA mutations (PIK3CAm+; E542K, E545K, H1047R, and N345K single nucleotide variants) or HER2 amplification (HER2 amp+; ERBB2 copy number >2.5). RESULTS: Median OS was 78.5 months [95% confidence interval (CI) 64.3-not reached (NR)] for eribulin and was NR for taxane, with a hazard ratio of 1.25 (95% CI 0.92-1.71, log-rank P = 0.19). The 60-month OS rates were 59.7% and 65.2% for eribulin and taxane, respectively. Median OS and 60-month OS rates were numerically lower in ctDNA PIK3CAm+ patients, and greater in ctDNA HER2 amp+ patients for all patients and with stratification by treatment group. There were no statistical interactions between treatment group with either ctDNA PIK3CAm or ctDNA HER2 amp status. Similar patterns were observed for PFS. CONCLUSION: Final survival analysis revealed that median OS exceeded 6 years with eribulin or physician-choice taxane, combined with trastuzumab plus pertuzumab, as first-line chemotherapy for HER2-positive LABC/MBC, with no significant differences between the two groups. ctDNA PIK3CAm+ status was a poor prognostic factor. ctDNA HER2 amp+ was associated with longer survival.

Aged↗
PubMed1992

[Hormone therapy using tamoxifen in unresectable carcinoma of the pancreas--preliminary study].

In 1981 Greenway and co-authors reported the existence of estrogen receptor in tumor tissue of the pancreas. We have tried hormone therapy using tamoxifen in 4 of 11 patients with unresectable carcinoma of the pancreas in whom expandable metallic stents were inserted for the palliation of obstructive jaundice. The mean survival period in these 4 patients was 235 days, and 2 of them had a remarkably long survival of 321 and 463 days respectively. On the other hand, the mean survival was 128 days in 7 control patients. We therefore evaluated this new therapy with tamoxifen as effective in patients with unresectable carcinoma of the pancreas.

Estrogens↗
PubMed1992

Roles of Langerhans' cells and T-lymphocytes infiltrating cancer tissues in patients treated by radiation therapy for cervical cancer.

Correlations between infiltration of immunologic cells in tumor tissues and prognosis of radiation therapy were investigated for 275 patients with cervical cancer who were treated with radiation therapy alone, including 216 patients with Stage III squamous cell carcinomas and 59 with adenocarcinomas of all stages. Langerhans' cell (LC) and T-cell were stained immunohistochemically on the specimens excised from the cervical cancer. In squamous cell carcinoma, 5-year survival rates for patients with LC infiltration were significantly better than those without LC (78% versus 60%; P < 0.01). The 5-year survival rate of patients with T-cell infiltration also was significantly better than that of patients without such infiltration (83% versus 61%; P < 0.05). Similar trends were observed in patients with adenocarcinoma; 5-year survival rates for patients with LC infiltration and those without LC infiltration were 49% and 25%, respectively (P < 0.025). The survival rates for patients with T-cell infiltration and those without were 50% and 33%, respectively (P < 0.1). An analysis of patterns of failure of radiation therapy demonstrated that the favorable prognosis in LC infiltration was attributable mainly to improvement of local control rates, but that in T-cell infiltration was not. T-cells infiltrated into tumor specifically in the patients with LC infiltration in both cell types. The authors suggest that the host anti-cancer immune response of individual patients may be remarkably different at the first step of antigen recognition by LC. The LC may induce T-cell-mediated antitumor response and improve local response in radiation therapy.

Adenocarcinoma↗
PubMed1992

Hepatotoxicity of trichlorfon and dichlorvos in isolated rat hepatocytes.

Hepatotoxicity of organophosphorus insecticides, trichlorofon and dichlorvos, a dechlorinated form of the former, was examined in isolated hepatocytes from untreated control and phenobarbital-pretreated (80 mg/kg, i.p., for 3 days) rats. These compounds produced toxic effects on hepatocytes as evidenced by malondialdehyde production and lactate dehydrogenase leakage in a dose-dependent manner up to the concentration of 2 mM, dichlorvos being more toxic than trichlorfon. Hepatocytes from phenobarbital-pretreated rats were more sensitive to these organophosphates than those from control rats. Dichloroacetaldehyde and dichloroacetic acid, metabolites of dichlorvos, did not injure hepatocytes. The toxic effects of dichlorvos on hepatocytes were enhanced by increasing oxygen concentration during the incubation, or by addition of glycolytic substrates (pyruvate, lactate or fructose) to the incubation mixtures. On the other hand, addition of antioxidants (diethyldithiocarbamate or N,N'-diphenyl-p-phenylenediamine), or cytochrome P-450 inhibitors (SKF-525A or metyrapone) to the incubation mixtures attenuated malondialdehyde production caused by dichlorvos and protected cells from death. Addition of dichlorvos to the incubation mixtures of hepatic microsomes stimulated lipid peroxidation in the presence of NADPH, which was inhibited by further addition of superoxide dismutase but not catalase. These results suggest that hepatotoxicity of trichlorfon and dichlorvos are related to their peroxidative property in microsomes which is accelerated by oxygen.

Animals↗
PubMed1992

Effects of feeding and fasting on hepatolobular distribution of glutathione and cadmium-induced hepatotoxicity.

Relationship between hepatolobular distribution profile of glutathione (GSH) and cadmium (Cd)-induced hepatotoxicity was examined in both fed and fasted rats by computerized densitometry of histochemically stained GSH in the liver sections using an image analyzer system. In fed rats, density gradient distribution of hepatolobular GSH, which was higher in the periportal region than in the perivenous one, was always observed even at a diurnally minimal concentration of GSH. This heterogeneous distribution of GSH, however, disappeared in fasted rats, even though the hepatic GSH concentration recovered to 81% of the control level in rats fasted for 48 h. In histopathological examination on livers 24 h after oral treatment of fed and fasted rats with 60 mg Cd/kg, zonal necrotic changes were observed from the perivenous to midlobular region but not in the periportal one in fed rats even at a diurnally minimal concentration of hepatic GSH. On the other hand, necrotic changes in the liver extended to the panlobular region including the periportal one in fasted rats. These necrotic changes were greater with a longer duration of fasting. These results suggest that the density gradient distribution of hepatic GSH but not the actual concentration of the compound plays an important role in protecting rats against acute hepatotoxicity of Cd.

Animals↗
PubMed1992

[Biliary endoprosthesis of malignant biliary obstruction using expandable metallic stent--preliminary clinical evaluation].

Thirty-eight patients with malignant biliary obstruction were treated with expandable metallic stent (EMS). Successful insertion of stents was attained in all cases, and in 34 of 38 patients, the stents remained patent and sufficiently expanded, and led to the removal of external drainage catheter. No serious complications occurred. In two cases, stents were deformed in shape, associated with no side effects. In follow-up, eleven patients developed recurrent jaundice due to tumor ingrowth between the wires and the tumor grew up along the initially placed stents. In six patients, additional stents were installed inside the initially placed stents, in whom the additional stents were placed successfully and remained patent thereafter. The expandable metallic stents were superior to the conventional tube stents, but there were some problems in our limited experience: stents deformity, slipping migration, fracture of stents and rapid obstruction. Further investigation is under way to resolve these problems. Long-term trials are required before established routine use of EMS. The expandable metallic stent was, however, expected to offer a new alternative in the management of malignant biliary obstructions and to afford long-term patency of affected biliary tracts.

Adult↗
PubMed1992

Genetic alteration of catecholamine specificity in transgenic mice.

Epinephrine-producing cells are characterized by the presence of phenylethanolamine N-methyltransferase (PNMT), which catalyzes the formation of epinephrine from norepinephrine. We generated a line of transgenic mice carrying a chimeric gene containing human PNMT cDNA fused to the 4-kilobase fragment of the human dopamine beta-hydroxylase (DBH) gene promoter, to switch catecholamine phenotype in the nervous and endocrine systems. Human PNMT transcripts and immunoreactivity were mainly detected in norepinephrine neurons in brain and sympathetic ganglion as well as in norepinephrine-producing cells in adrenal medulla of transgenic mice, indicating that the human DBH gene promoter of 4 kilobases is sufficient to direct expression of the gene in norepinephrine-producing cells. Analysis of catecholamines in the various tissues showed that the expression of human PNMT in transgenic mice induced the appearance of epinephrine in sympathetic ganglion and dramatic changes in norepinephrine and epinephrine levels in brain, adrenal gland, and blood. These results indicate that the additional PNMT expression in norepinephrine-producing cells can convert these cells to the epinephrine phenotype, and suggest that norepinephrine-producing cells normally possess the basic machinery required for the synthesis of epinephrine except for PNMT. Thus it appears that the only major difference between norepinephrine- and epinephrine-producing cells is the expression of PNMT. Our transgenic animals provide an experimental model to investigate the functional differences between norepinephrine and epinephrine.

Animals↗
PubMed1992

High-dose-rate remote afterloading intracavitary radiation therapy for cancer of the uterine cervix. A 20-year experience.

Retrospective analysis was performed on 1022 patients with squamous cell carcinoma of the uterine cervix who were treated with high-dose-rate remote afterloading intracavitary irradiation at the National Institute of Radiological Sciences, Angawa, Chiba-shi, Japan, from 1968 to 1982 in comparison with low-dose-rate intracavitary radiation therapy. The patient population consisted of 147 patients with Stage I disease, 256 patients with Stage II disease, 515 patients with Stage III disease, and 104 patients with Stage IV disease. Absolute 5-year survival rates for Stages Ib, IIa, IIb, IIIb, IVa, and IVb disease were 88.1%, 76.9%, 67.0%, 52.2%, 24.1%, and 13.3%, respectively. The rates of severe complication of Grades 3 and 4 were 4.1% for the rectosigmoid colon, 1.2% for the bladder, and 1.1% for the small intestine. In the case of Stage I to II disease, the optimal dose from intracavitary sources was suggested to be 2900 cGy +/- 200 cGy at point A, with 4 to 5 fractions of 600 to 700 cGy delivered over 4 to 5 weeks. These results suggested that high-dose-rate intracavitary radiation therapy provided clinical results comparable to those of a low-dose-rate technique.

Adult↗
PubMed1992

Adhesive bone cement containing hydroxyapatite particle as bone compatible filler.

Acrylic bone cement containing hydroxyapatite (HA) as a filler was developed using 4-methacryloyloxyethyl trimellitate anhydride (4-META) to promote adhesion both to bone and HA. The mechanical strengths of the cement did not decrease significantly with increasing HA in the cement by 4-META. However, strengths decreased with increasing HA content in the absence of 4-META. Scanning electron micrographic examination of fractured surfaces of the cement clearly showed that the HA particles adhered to the matrix resin when 4-META was added. Thus, it was important to maintain the original mechanical strengths for 4-META. The HA particles along the surface increased with increased HA content in the cement. The cement adhered to bone with a tensile bond strength was higher than 10 MPa.

Acrylic Resins↗
PubMed1992

Comparative teratogenicity of di-n-butyltin diacetate with n-butyltin trichloride in rats.

Teratological tests were conducted on di-n-butyltin diacetate (DBTA), and n-butyltin trichloride (MBTC). Pregnant Wistar rats were treated orally with DBTA at doses of 0, 1.7, 5.0, 10.0, and 15.0 mg/kg/day or with MBTC at doses of 0, 50, 100, 200, and 400 mg/kg/day during days 7-17 of gestation. Cesarean sections were performed on day 20 of gestation. Thymic atrophy of the pregnant rats was observed in a dose-dependent manner by DBTA treatment. The incidence of dead or resorbed fetuses and total resorption fetuses increased at the highest dose of DBTA. The incidence of fetuses with external malformations, such as cleft mandible, cleft lower lip, ankyloglossia (tongue-tie) and schistoglossia (cleft tongue), increased in a dose-dependent manner by DBTA treatment. The incidence of fetuses with skeletal malformations such as anomaly of mandibular fixation, fused ribs, fused cervical vertebral arches and fused thoracic vertebral arches also increased at 10.0 and 15.0 mg/kg. However, MBTC, one of the main metabolites of di-n-butyltin, failed to show any evidence of tetatogenic activity at any doses tested. The results indicate that DBTA has potent teratogenic effects on rat fetuses, and DBTA is different from MBTC with respect to teratogenic effects.

Animals↗
PubMed1992

Clinical trial of FK 506 immunosuppression in adult cardiac transplantation.

The new immunosuppressive agent FK 506 was used as primary immunotherapy in conjunction with low-dose steroids and azathioprine in 72 patients subsequent to orthotopic cardiac transplantation. Overall patient survival at a mean follow-up of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or greater) within 90 days of transplantation was 0.95 per patient. The actuarial freedom from rejection at 90 days was 41%. Achievement of this level of immunosuppression is comparable with that of cyclosporine-based triple-drug therapy with OKT3 immunoprophylaxis. Thirty percent of patients were tapered off all steroids, and the average steroid dose in the group who received steroids was 8.6 mg of prednisone per day. The incidence of infection reflected the diminished necessity for steroids: seven major infections (10%) and 11 minor infections (16%). Renal dysfunction occurred during the perioperative period in most patients in this trial. However, the incidence of hypertension was 54% compared with 70% during the cyclosporine era. Ten adults underwent successful rescue therapy with FK 506 after cardiac rejection refractory to conventional immunotherapy. Side effects of FK 506 were notably few, and the results of the trial are encouraging for the future of the cardiac transplant recipient.

Adult↗
PubMed1992

Detection of HIV-1 RNA in heparinized plasma of HIV-1 seropositive individuals.

The interference of reverse transcription by heparin was removed by heparinase. When the HIV-1 RNA in the presence of heparin was detected by a combination of reverse transcription and the polymerase chain reaction (PCR), heparinase treatment followed by removal of Ca2+ before the reverse transcription step permitted the efficient detection of HIV-1 RNA. Prior treatment with heparinase revealed HIV-1 RNA in 68% (13/19) of heparinized plasma samples from HIV-1 carriers, whereas only 26% (5/19) of the same specimens were positive without the heparinase step. Heparinase removed the inhibition of reverse transcription by heparin and is highly recommended when detecting low levels of viral RNA in heparinized plasma.

HIV Reverse Transcriptase↗
PubMed1992

Organization and complete nucleotide sequence of the gene encoding mouse phenylethanolamine N-methyltransferase.

Phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28) catalyzes the conversion of norepinephrine to epinephrine, the last step of catecholamine biosynthesis. We have previously reported molecular cloning of cDNA encoding human PNMT and chromosomal localization of its gene (Kaneda et al., J. Biol. Chem., 263 (1988) 7672-7677). In this report, we isolated the chromosomal gene encoding mouse PNMT by cross-hybridization with the human PNMT cDNA. Mouse PNMT gene spanned about 1.8 kb and consisted of 3 exons. Primer extension analysis showed two putative transcription initiation sites. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of the mouse PNMT mRNA in brain (pons and medulla oblongata) and adrenal gland. Subsequently cDNA encoding mouse PNMT was amplified by RT-PCR and cloned into the plasmid vector. Mouse PMNT gene contained the protein-coding region of 885 bp (295 amino acids) with the predicted molecular weight of 32,627. The deduced amino acid sequence of mouse PNMT revealed the major difference in the N-terminal region, as compared to the human and bovine PNMT sequences. In the 5'-terminal region of the mouse PNMT gene, we found the existence of 23 bp direct repeat sequences, which was not observed in the corresponding regions of the human and bovine PNMT genes. The presence or absence of the direct repeats caused the major difference in the PNMT sequences among species. The typical TATA, GC, and CACCC boxes as well as several sequences homologous to glucocorticoids response elements (GRE) were located in the 5'-flanking region of the mouse PNMT gene.

Amino Acid Sequence↗
PubMed1992

Role of gastric glutathione in smoke flavouring-induced gastric injury in rats.

Some commercial liquid smoke flavourings have been shown to induce acute gastric mucosal injury in rats when given orally as a large single dose. The present study was carried out to examine the mechanism of action in rats of two selected smoke flavourings containing about 10% total acids as acetic acid. These flavourings and 10% acetic acid decreased the concentration of glutathione (GSH) in the glandular stomach. The decrease in gastric GSH was coupled with smoke flavouring-induced gastric injury. Pretreatment with N-ethylmaleimide, a GSH depletor, enhanced acetic acid-induced gastric injury. Pretreatment with cysteine, a sulphhydryl compound, protected rats against smoke flavouring-induced gastric injury. Aqueous fractions of the smoke flavourings, after removal of non-polar compounds and acidic organic compounds (including acetic acid) by diethyl ether extraction, decreased the gastric GSH concentration considerably and had a marked reactivity in vitro with GSH, but these fractions by themselves showed no ability to induce gastric injury. Addition of 10% acetic acid to these aqueous fractions caused greater gastric injury than 10% acetic acid alone, which suggests that these aqueous fractions contain the (unidentified) compound(s) that facilitate acetic acid-induced gastric injury. These findings indicate that gastric endogenous and exogenous sulphhydryls play an important part in gastric cytoprotection.

Acetates↗
PubMed1992

Indications of particle radiation therapy in the treatment of carcinoma of the esophagus.

Studies were made to evaluate the role of radiations in the treatment of carcinoma of the esophagus to confirm indications for charged particles. Results of the studies showed that prognosis of the patients treated with radiations depend strongly on length of tumor as well as on invasion of tumor cells into the adventitia of the esophagus. It was concluded that patients suffering from carcinoma of the esophagus less than 8 cm length are indicated for particle radiations.

Esophageal Neoplasms↗
PubMed1992

Combination therapy of local administration of OK-432 and radiation for esophageal cancer.

Local administration of OK-432, a biological response modifier, was combined with radiation in 30 patients with esophageal cancer as a pilot study. Complete response was obtained in 22 of 30 patients (73.3%); and partial response was obtained in the remaining eight cases (26.7%). Complete response was obtained in all eight patients with a tumor less than 5 cm in length. In the group with tumors 5-10 cm in length, complete response was obtained in 11 of 14 cases (78.6%); and partial response was obtained in 3 of 14 cases. In the group with a tumor length of more than 10 cm, complete response was obtained in 3 of 8 cases (37.5%); and partial response was obtained in 5 of 8 cases. One-year, 2-year, and 3-year survival rates of the 30 patients, including four patients who died of other diseases, were 67.9%, 40.8% and 29.0%, respectively. This new combination therapy may contribute not only to local control, but also to survival.

Aged↗
PubMed1992

Regional differences in myosin heavy chain isoforms and enzyme activities of the rat diaphragm.

Myosin heavy chain isoforms and enzyme activities were compared between the costal and crural regions of the rat diaphragm. The percentage of heavy chain (HC) IIb in the crural region of the diaphragm was significantly (P less than 0.05) higher than that in the costal region (mean 7.3 vs. 3.0%), and the percentage of HCI was significantly lower in the crural than in the costal diaphragm (22.7 vs. 27.9%). The distributions of HCIIa and HCIId were relatively homogeneous in both regions. Succinate dehydrogenase activity in the costal diaphragm was 21% greater (P less than 0.01) than in the crural diaphragm. In contrast, there was no significant difference in the activity of phosphofructokinase in the crural and costal diaphragms. These results demonstrate that a difference in myosin heavy chain isoforms and oxidative capacity exists between the costal and crural regions of the rat diaphragm.

Animals↗