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Biomedical subjects

T Takano

Publications and source records attributed to T Takano.

15 recordsLinked to original sources

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

Mutagenic activity of selenium compounds.

The mutagenicities of selenate (SeO2/4-) and selenite (SeO2/3-) were determined by two bacterial assay systems: Kada's rec-assay and Ames's Salmonella test. In both assays, these compounds were found to be weak mutagens. In the Salmonella test, selenate (0.05 revertants/nmole) and selenite (0.2 revertants/nmole) gave rise to base-pair substitution.

Bacillus subtilis

Evidence for bactericidal activity of polymorphonuclear leukocytes without phagocytosis.

The relationship between phagocytosis and bactericidal action of polymorphonuclear leukocytes was examined by comparing the functions of cytochalasin D-treated leukocytes with those of the control. Measurement of phagocytotic and bacterial DNA-degrading activities using Escherichia coli prelabeled with [3H]thymidine revealed that phagocytosis and bacterial DNA degradation were inhibited by treatment with cytochalasin D to about 50 and 10% of the control, respectively. Nevertheless, the bactericidal activity of the cytochalasin D-treated leukocytes was almost the same as that of the control leukocytes; almost all the bacteria were phagocytized by the latter leukocytes. Under the same experimental conditions, the production and release of superoxide anions and hydrogen peroxide, which are both known to be involved in the bactericidal action of the leukocytes, were markedly increased by cytochalasin D. Release of several lysosomal hydrolases was also increased markedly by cytochalasin D treatment, except for myeloperoxidase. However, lactate dehydrogenase, a typical cytosolic marker, was not released by the same treatment. Thus, it is unlikely that the increase in the release of the above-mentioned bactericidal factors was due to decomposition of the leukocytes. These results indicate that the site of bactericidal action of cytochalasin D-treated leukocytes is not necessarily intracellular but may be around the external surface of the cells.

Animals

Tuna cytochrome c at 2.0 A resolution. II. Ferrocytochrome structure analysis.

The x-ray crystal structure analysis of tuna ferrocytochrome c has been extended from 2.45 to 2.0 A resolution. The overall folding is unchanged and is the same as has been reported for tuna ferricytochrome c (Swanson R., Trus, B.L., Mandel, N., Mandel, G., Kallai, O.B., and Dickerson, R.E. (1977) J. Biol. Chem. 252, 759-755). No significant structural differences are observed between oxidation states. Difference map studies using reoxidized crystals of ferrocytochrome c confirm the absence of a conformation change. A detailed analysis of hydrogen bonding shows the presence of six beta or 310 bends of type II with obligatory glycines in the 3rd residue position. This explains 6 of the 10 nearly invariant glycines in the molecule. Close packing contacts account for three more, and only the invariant glycine 1 remains a mystery.

Amino Acid Sequence

Endogenous carbon monoxide production in alloxanized rats.

The endogenous production of carbon monoxide (Vco) in thirty-three diabetic rats induced by alloxan and in fifteen normal rats was measured by serial determinations of the expired carbon monoxide and of the increase of carbon monoxide in the blood during rebreathing in a closed system. Vco (mean +/- S.E., micronl/250g/hr) in the group of alloxanized rats 24, 48, 72, 96, 120 and over 144 hours after the alloxan injection was 6.2 +/- 2.9, 8.4 +/- 2.1, +/- 1.8, 10.7 +/- 3.5, 16.4 +/- 2.0 and 16.5 +/- 2.2, respectively, whereas it was 5.9 +/- 0.4 for the control. This indicates that the alloxanized group maintaining a high blood sugar level for over 120 hours has a three-fold higher Vco than the control.

Animals

Histotoxic properties of carbon monoxide in the living organ I. Fluorometry of oxidation-reduction state of the rabbit kidney in situ.

Effect of carbon monoxide on the redox state and blood flow in the renal cortex of the rabbit was examined by the fluorometric method. By a short-period (1-3 min) inhalation of CO in concentrations over 1%, the following were revealed: (1) Reduced pyridine nucleotide was increased, (2) oscillatory change of the reduced pyridine nucleotide, which is characteristic for the histotoxic reaction, developed, and (3) extent of the fluorescence changes tended to be in proportion to the concentration of CO, but no change was caused by inhalation of CO in lower concentrations (0.1%, 0.5%) even if the inhalation was continued for 30 min. As to the blood flow, CO in concentrations over 0.5% decreased it, whereas anoxia due to nitrogen increased it. Some implications were discussed from toxicological points of view on the results obtained.

Animals

Metabolic and cardiovascular abnormalities in patients with peripheral arterial disease.

Twenty-eight consecutive patients of an average age of 63 years with intermittent claudication secondary to underlying peripheral arterial disease were studied for evidence of metabolic or other cardiovascular abnormalities and the results obtained were compared with those of 28 matched control subjects free of vascular disease. Patients with peripheral arterial disease had significantly higher levels of systolic and diastolic blood pressure, a greater incidence of ECG abnormalities, lipoprotein abnormalities, elevated serum triglycerides, and serum copper. The incidence of smoking and abnormal glucose tolerance, while higher in peripheral arterial disease patients, was not statistically significant. Hematocrit and serum cholesterol levels were nearly indentical in both groups of patients. Twenty-six of the 28 patiens with peripheral arterial disease had either a cardiovascular or a metabolic abnormality, indicating the high incidence of multisystem illness in this disorder. The epidemiologic data in peripheral arterial disease are similar to those in coronary artery disease but some measurements contrast sharply, such as the apparent normal level of serum cholesterol in patients with peripheral arterial diseases.

Adult

Fate of viral RNA of murine leukemia virus after infection.

[3H]Uridine-labeled Rauscher leukemia virus was used to infect mouse embryo fibroblasts. After the infected cells were separated into nuclear and cytoplasmic fractions nucleic acid was extracted by sodium dodecyl sulfate-phenol-chloroform treatment and analyzed by Cs2SO4 and sucrose density gradient centrifugation. Between 45 and 70 min after infection a transient and synchronized shift of the acid-insoluble radioactive peak toward the RNA-DNA hybrid region occurred in both the nuclear and cytoplasmic fractions. The density of the cytoplasmic hybrid shifted to 1.56 g/ml (RNA equals about 50%), while the sedimentation rate decreased from 36 S to 14 S; however, the density of the nuclear hybrid shifted to 1.58-1.48 g/ml (RNA equals 57-17%, respectively), while its sedimentation rate remained about 65 S. The hybrids in both the nuclear and the cytoplasmic fractions still showed hybrid density after heat denaturation. The processes of the early stages of RNA tumor virus infection are discussed with regard to the functions of viral RNA-dependent DNA polymerase (reverse transcriptase) and a possible integration of viral genetic information into the host chromosome.

Animals

Subclavian steal in Takayasu's arteritis. A hemodynamic study by means of ultrasonic Doppler flowmetry.

Blood flow in the vertebral artery and the upper extremity was studied in five cases of Takayasu's arteritis with subclavian steal by use of ultrasonic Doppler flowmetry and finger plethysmography. The diagnosis of subclavian steal was made by observation of flow reversal in the vertebral artery on the subclavian steal side during grip exercise and, in addition, the vertebral flow change with brachial artery occlusion. The blood flow increase of both internal cartotid and non-affected (non-subclavian steal side) vertebral arteries during a common carotid compression was almost normal in patients with Takayasu's arteritis in this study. During carotid compression on the side of the subclavian steal, ipsilateral vertebral blood flow greatly decreased, and the amplitude the ipsilateral finger plethysmogram decreased slightly or moderately. It is suggested that there are significantly important factors in suppressing sumptoms of vertebrobasilar ischemia in these patients with Takayasu's arteritis with subclavian steal. These factors are believed to be (1) good function of the circle of Willis, (2) good blood supply to the brain stem, and (3) collateral circulation to the distal subclavian artery not via the vertebral artery.

Aortic Arch Syndromes