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T Takano

Publications and source records attributed to T Takano.

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↗
PubMed1995

Spatial and temporal regulation of the rat calmodulin gene III directed by a 877-base promoter and 103-base leader segment in the mature and embryonal central nervous system of transgenic mice.

Three non-allelic rat calmodulin (CaM) genes CaMI, CaMII and CaMIII, which share no homology in their 5'-upstream regions, are coordinately expressed in neurons of the central nervous system (CNS). Deletion analysis of the CaMIII promoter showed that the upstream segments longer than 700 bases functioned as efficient promoters, and that the sequence from -133 to -65 was required for the activity of house-keeping type promoter in transient expression assays on a mouse glioma cell line C6. However, the transient expression seemed not to be cell type specific. To determine the temporal and spatial specificity of the promoter function, we produced transgenic mice carrying a fusion gene of the CaMIII segment from -877 to +103 and the lacZ reporter gene. In CNS of the adult transgenic mice, the localization of transgene expression was similar to that of endogenous CaMIII transcripts analyzed by in situ hybridization. The transgene was expressed prominently in pyramidal cells of the cerebral neocortex and the hippocampal regions CA1 to CA3, in Purkinje cells of the cerebellar cortex, and in neurons of the spinal cord, and moderately in granule cells of the dentate gyrus and the cerebellar cortex. In the developing CNS, the overall profiles of neuron-specific expression were also similar for both transgene and endogenous CaMIII that were expressed in the mantle layer and the dorsal root ganglia of the embryonal spinal cord. These results indicated that the neuron-specific expression of rat CaMIII was directed by this 877-base promoter sequence. The CaMIII segment used for the promoter of transgene contained a 29-bp sequence at -410, namely H3, which was conserved in the upstream regions of vertebrate CaMII and CaMIII. H3 seemed to play a pivotal role in the temporal and spatial expression of transgene in CNS, although the deletion of H3 did not decrease CAT activity in the transient expression. The transgene expression was not observed in the external granular cells of the developing cerebellum and in some neurons of the embryonic sensory ganglia in which the endogenous CaMIII was obviously expressed. Therefore, the other cis-acting element(s) located outside of this 877-bp segment seemed to be required for the temporal regulation of CaMIII in certain rudimentary neurons.

Animals↗
PubMed1995

Effect of ethanol on nitrite oxidation in the perfused rat liver.

The effect of ethanol on nitrite oxidation was investigated in the perfused rat liver. Real-time spectral changes in catalase were obtained using a reflectance scanning spectrophotometer in rat liver perfused with Krebs-Henseleit bicarbonate buffer in a non-recirculating system. The nitrite oxidation rate and nitrate production rate were calculated from the differences in concentrations between the influx and efflux perfusates and from the flow rate/g liver weight. Nitrite infusion caused an increase in absorbance difference delta A (640-660 nm), indicating decomposition of catalase compound I to the free form. Administration of ethanol during the nitrite infusion caused a further increase in delta A (640-660 nm) and significant decreases in both the nitrite oxidation rate and the nitrate production rate. Both the nitrite oxidation rate and nitrate production rate decreased, depending on the concentration of ethanol administered. At 10 mM ethanol, they reached about half the rates before the ethanol infusion. In conclusion, ethanol inhibits nitrite oxidation by catalase in the perfused rat liver at relatively low concentrations that can be realized in blood by daily alcohol consumption.

Animals↗
PubMed1995

Sleep habits and psychosomatic health complaints of bank workers in a megacity in Japan.

The relationship between sleep habits and psychosomatic health complaints was investigated by a questionnaire study in 148 bank workers in Tokyo. Daily bedtime was more flexible than daily rising time, and both mean bedtime and rising time tended to be earlier with increasing age. Multiple logistic regression analysis showed that psychosomatic health complaints of sleep disturbances, fatigue, digestive troubles, and depressive mood were significantly associated with sleep habits and perceived mental stress.

Adolescent↗
PubMed1995

Effects of simultaneous administration of ethanol on styrene metabolism under fed and fasted conditions in the perfused rat liver.

The purpose of this study was to clarify the simultaneous administration of ethanol on styrene metabolism in the perfused rat liver under fed and fasted conditions. Styrene uptake rate, production rate of styrene glycol, oxygen consumption rate, and changes in reduced pyridine nucleotide fluorescence were monitored in the perfused rat liver. The effects of ethanol on parameters of styrene metabolism were observed in rat livers under fed and fasted conditions: fed (group I), fasted (group II), and fasted with xylitol in the perfusate (group III). The simultaneous administration of ethanol and styrene significantly decreased styrene uptake rate, production rate of styrene glycol, and oxygen consumption rate, and produced significant reduction of pyridine nucleotide fluorescence as compared with the single administration of styrene in groups I and III. In contrast, the simultaneous administration of ethanol and styrene significantly increased the production of styrene glycol and oxygen consumption as compared with the single administration of styrene in group II. Significant effects on the styrene uptake rate and the reduced pyridine nucleotide fluorescence were observed with regard to factors of both nutritional status and the interaction between ethanol and nutritional status by two-way analysis of variance. These findings showed that the effects of ethanol on styrene metabolism in the liver were dependent upon the nutritional status of the animal. The fed and fasted conditions affected the effect of ethanol on styrene metabolism by changing the supply of NADPH to the mixed-function oxidase system. In conclusion, ethanol suppressed styrene metabolism in the fed condition, but enhanced it in the fasted condition. This phenomenon should be considered in the prevention of occupational hazard of styrene exposure in industrial workers with alcohol drinking habits and nutritional problems.

Animals↗
PubMed1995

The effect of lansoprazole treatment on the healing and relapse of peptic ulcer and serum levels of IgG anti-Helicobacter pylori antibody.

In the present study, the effects of short-term treatment with lansoprazole on healing and recurrence of peptic ulcer were investigated. Complete healing (change to the S2 stage) after 3 or 4 weeks of treatment with lansoprazole was observed in 9.9% of gastric ulcers and 38.3% of duodenal ulcers. Complete healing was observed after 3 or 4 weeks of treatment with lansoprazole in gastric ulcers and was significantly related to the serum titer of IgG anti-Helicobacter pylori antibodies. This was not the case in duodenal ulcers. Complete healing after 6 or 8 weeks of treatment with lansoprazole was not dependent on serum levels of IgG anti-H. pylori antibodies. Short-term treatment by lansoprazole did not affect serum levels of IgG anti-H. pylori antibodies immediately after the end of lansoprazole treatment, but significantly reduced serum levels of IgG anti-H. pylori antibodies were found 9 months after treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

The endothelium in glomerular inflammation.

Endothelial activation is central to the pathophysiology of glomerulonephritis, vasculitis, allograft rejection, ischemia-reperfusion injury and thrombotic angiopathies. Major advances in endothelial biology during the past year have emphasized the importance of selectin, mucin, integrin, and immunoglobulin-like adhesion molecules in leukocyte trafficking in glomerular inflammation, and have defined novel mechanisms by which leukocyte-endothelial cell interactions are regulated by inflammatory mediators and cytokines. These breakthroughs have already spawned experimental immunosuppressive strategies that should antecede the development of novel, potent and specific therapies for common renal diseases.

Animals↗
PubMed1995

Origin and pathophysiological role of increased plasma endothelin-1 in patients with acute myocardial infarction.

To investigate the origin and pathophysiological role of increased plasma endothelin-1 (endothelin-1) concentration in patients with acute myocardial infarction (AMI), the authors measured plasma endothelin-1 sequentially after the onset of AMI and analyzed the origin by the simultaneously obtained blood samples from the radial artery, right atrium, and pulmonary artery in 28 patients with AMI. The data were correlated with cardiovascular hemodynamics, infarct size, and coronary arteriographic findings. Arterial endothelin-1 at twenty-four and seventy-two hours significantly correlated with mean pulmonary arterial pressure (r = 0.48, r = 0.46, P < 0.05, respectively), central venous pressure (r = 0.42 and 0.51, P < 0.05, respectively), and pulmonary vascular resistance (r = 0.42, r = 0.42, P < 0.05), and endothelin-1 at one hundred twenty hour significantly correlated with peak creatine kinase (r = 0.53, P < 0.05) and creatine kinase isozyme MB (r = 0.58, P < 0.01). Simultaneous blood samples showed no significant difference in endothelin-1 concentrations among them. However, a subgroup of patients with endothelin-1 concenration higher in the radial artery than that in the right atrium showed a significantly higher mean pulmonary arterial pressure (25.2 +/- 6.5 vs 17.0 +/- 1.6 mmHg, P < 0.05), peak creatine kinase (3594 +/- 1597 vs 865 +/- 495 IU/L, P < 0.05), and peak creatine kinase MB (214 +/- 91 vs 69 +/- 22 IU/L, P < 0.05) as compared with those in patients in whom endothelin-1 was higher in the right atrium than in the radial artery. Increased plasma endothelin-1 concentration in the early stage of AMI reflects higher pulmonary artery pressure and elevated pulmonary vascular resistance, while that in the later stage is related to the infarct size. The production of endothelin-1 in patients with severe pump failure may be accerelated in the pulmonary vascular bed, left ventricle, or systemic arterial trees, and the main origin in the later stage is possibly coronary vasculature in the infarcted area.

Aged↗
PubMed1995

Follow-up of 2,733 Japanese patients with myocardial infarction.

Two thousand, seven hundred and thirty-three patients with acute myocardial infarction (AMI) who were admitted to our 11 institutions between 1983 and 1988, examined by coronary arteriography and discharged alive, were followed for an average of 2.9 years. During the follow-up period, 212 patients (7.6%) died. The factors that governed the prognosis of myocardial infarction after discharge were advanced age, female gender, obesity, previous infarction, angina pectoris more than 1 month before the onset of AMI, post-infarction angina, multiple-vessel diseases, advanced stage by Killip's and/or Forrester's classification on admission, elevated pulmonary capillary arterial pressure, decreased cardiac index, decreased left ventricular ejection fraction, increased left ventricular end-diastolic volume and left ventricular aneurysm before hospital discharge. Patients with ventricular tachycardia or ventricular fibrillation during hospitalization showed a poor prognosis. In contrast, patients who received intracoronary thrombolysis, or emergent and/or elective percutaneous transluminal coronary angioplasty showed a favorable prognosis.

Adult↗
PubMed1995

Factors governing re-infarction in patients with myocardial infarction in Japan.

The subjects consisted of 2,733 patients with acute myocardial infarction (AMI) who were admitted to our 11 institutions between 1983 and 1988, examined by coronary arteriography, and discharged alive. The patients were followed for an average of 2.9 years after discharge. During the follow-up period, re-infarction occurred in 172 patients (6.3%). The factors associated with re-infarction were total cholesterol of more than 250 mg/dl, HDL-cholesterol of less than 35 mg/dl and diabetes mellitus. The rate of re-infarction was also high in patients who had had a previous infarction before admission, angina pectoris before or after the onset of AMI or multiple-vessel disease. In contrast, intracoronary thrombolysis reduced the rate of re-infarction.

Angina Pectoris↗
PubMed1994

Staurosporine can inhibit the G1-S transition induced by a calcium channel agonist by blocking the pathway independent of phorbol ester-sensitive protein kinase C in rat thyroid cells (FRTL-5).

IGF-I, when added to TSH-primed FRTL-5 cells, can induce a long lasting Ca2+ influx followed by the DNA synthesis. BAY K8644, a Ca2+ channel agonist, can also induce the DNA synthesis in TSH-treated cells. Staurosporine, which is known to be a potent inhibitor of protein kinase C(PKC) strongly inhibited the DNA synthesis caused by these two reagents. However, in PKC-down regulated cells, IGF-I and BAY K8644 could also evoke the DNA synthesis and the inhibitory effect of staurosporine persisted. These inhibitory effects did not relay on inhibition of the Ca2+ influx induced by BAY K8644. Thus these results demonstrate that staurosporine acts at a point distal to Ca2+ influx to inhibit G1-S transition and this staurosporine-sensitive pathway possibly mediates the mitogenic signal in PKC-independent manner.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Loss of collagenase gene expression in immortalized clones of SV40 T antigen-transformed human diploid fibroblasts.

We isolated a cDNA clone whose expression was lost during immortalization. The subtractive hybridization was performed between a genetically matched pair of mortal and immortal lines of SV40 T antigen-transformed MRC-5. The clone was found to code human interstitial collagenase. The expression of collagenase gene was almost completely shut off in seven out of eight independent immortalized clones. In addition, the levels of collagenase expression were dramatically increased toward crisis in the T antigen-transformed but mortal cells. These findings suggest the possibility that the regulatory mechanism of collagenase expression is related to both processes of in vitro aging and immortalization.

Antigens, Polyomavirus Transforming↗
PubMed1992

Four synonymous genes encode calmodulin in the teleost fish, medaka (Oryzias latipes): conservation of the multigene one-protein principle.

We cloned four distinct calmodulin (CaM)-encoding cDNAs from a small teleost fish, medaka (Oryzias latipes). The deduced amino acid (aa) sequences were exactly the same in these four genes and identical to the aa sequence of mammalian CaM, because of synonymous codon usages. The four cDNAs from medaka, termed CaM-A, -B, -C and -D, corresponded to mRNAs of 1.8, 1.4, 2.5 and 1.8 kb, respectively, in Northern blot analysis. Our results demonstrated that the 'multigene one-protein' principle of CaM synthesis is applicable to medaka, as well as to mammals whose CaM is encoded by at least three different genes.

Amino Acid Sequence↗
PubMed1992

Expression of platelet activating factor receptor in renal tubular cell line (LLC-PK1).

Northern blot analyses of poly(A)+ RNA extracted from cloned renal tubule cells, LLC-PK1, MDCK and JTC-12 cells, were performed using an isolated cDNA of guinea pig platelet activating factor (PAF) receptor as a probe. The results showed the expression of single entity of PAF receptor mRNA in LLC-PK1, but not in MDCK or JTC-12 cells. PAF also induced a dose-dependent elevation of intracellular calcium in LLC-PK1 cells as assessed by Fura-2 fluorescence signals, which was completely blocked by a PAF receptor antagonist, WEB 2170. These results indicate a PAF receptor-effector system in a renal tubular cell line LLC-PK1, providing a possible model system for studying physiological roles of PAF receptors in renal tubules.

Animals↗