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Biomedical subjects

S Kubo

Publications and source records attributed to S Kubo.

14 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

Light chains of chicken embryonic gizzard myosin.

1. Myosin from gizzards of 15-day-old chicken embryos was highly purified by ammonium sulfate fractionation in the presence of ATP and MgCl2, ultra-centrifugation and Sepharose 4B chromatography. 2. The myosin composed of heavy and three light chains as determined by sodium dodecyl sulfate (SDS) gel electrophoresis. The molecular weights of the light chains were 23,000 (L23), 20,000 (L20), and 17,000 (L17), respectively. The amount of L23 light chain decreased and disappeared, and the L17 light chain increased steadily in the course of development. The amount of L20 light chain did not change. 3. ATPase activity of the embryonic myosin was essentially the same as that of adult myosin. The change in the light chain pattern in the course of development did not correlate to the ATPase activity. 4. Antigenicity of the heavy chains in the embryonic myosin was the same as that of the adult heavy chains. However, antibodies to light chains were not detected in the antibodies to either the embryonic or adult myosins.

Adenosine Triphosphatases

Purification and some properties of rabbit stomach myosin.

Myosin from rabbit stomach was highly purified by ammonium sulfate fractionation in the presence of ATP and MgCl2, ultracentrifugation and Sepharose 4B chromatography. The myosin composed of one heavy and two light chains as determined by SDS-gel electrophoresis. The molecular weights of the light chains were the same as those of gizzard myosin, about 20,000 and 17,000, respectively. The pH-activity curve and the KCl concentration dependency of Ca-ATPase of the stomach myosin were similar to those of other smooth muscle myosins. The stomach myosin was more resistant to pepsin digestion than skeletal myosin. Other proteolytic enzymes, trypsin, chymotrypsin, papain, and nagarse, digested the myosin in the same way as skeletal myosin.

Adenosine Triphosphatases

Comparative studies on 5,5'-dithiobis-(2-nitrobenzioc acid)-treated myosins.

Myosins prepared from chicken and rabbit fast and slow muscles were treated with 5,5'-dithiobis-(2-nitrobenzoic acid) (Nbs2). About half of the thiol groups of the fast muslce myosins reacted with Nbs 2, but in slow muscle myosins, only about 10-20% of the thiol groups reacted. This treatment removed 50-60% of the L2 components, Nbs2 light chain, from fast muscle myosins, but did not result in specific dissociation of the light chains in slow myscle myosins. The treatment sometimes released L4 component from chicken muscle myosins instead of L2 component. The changes of myosin ATPase [EC 3.6.1.3] activities caused by this treatment did not correlate with the release of Nbs2 light chain, but were dependent upon the species, chicken or rabbit.

Adenosine Triphosphatases

Pharmacological studies of 1-(o-chlorophenyl)-2-tert.-butylaminoethanol (C-78), a new bonchodilator.

The bronchodilating effects and other related pharmacological properties of 1-(o-chlorophenyl)-2-tert.-butylaminoethanol-hydrochloride (C-78) were studied in comparison with those of isoproterenol, salbutamol and clorprenaline. C-78 was found to produce a bronchodilating effect 2--10 times stronger and considerably weaker than clorprenaline and isoproterenol, respectively. However, the bronchodilating effect of C-78 was sustained more than 10 times as long as those of isoproterenol and sulbutamol and, especially on oral administration, it was much more potent. The bronchodilating effect of C-78 seems to be due to excitation of the adrenergic beta-receptor, and was antagonized by propranolol. The positive chronotropic and inotropic effects of C-78 on an isolated atrial preparation were less than 1/1000 as potent as those of isoproterenol. C-78 also decreased the tone of smooth muscle, such as the uterus, but its affinity for the bronchial muscle is much higher than for the uterus. C-78 showed strong anti-anaphylactic action and strongly promoted the tracheal ciliary movement. Anitussive effect was also demonstrated, though this was inferior to that of codeine, however, there was no influence on bronchosecretion.

Acetylcholine