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Biomedical subjects

A Kato

Publications and source records attributed to A Kato.

7 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

Extensive hepatic cell necrosis produced by the Shwartzman mechanism.

Acute, severe, and extensive necrosis of the liver was produced in pregnant and non-pregnant female adult rabbits by the Shwartzman mechanism. Shwartzman reagent (E. coli endotoxin) was administered in various combinations by three routes of injection, the portal vein (mesenteric vein), the bile duct, and the ear vein. Morphologic changes of the extrahepatic organs were minimal. The similarity to massive necrosis in human liver and the effect of pregnancy on hepatic necrosis in rabbit and man were discussed. The lesion is presented as a new animal model for acute massive hepatic necrosis and is proposed as a third category of Shwartzman reaction, designated the univisceral type.

Acute Disease

In vitro maturation of mesencephalic dopaminergic neurons from mouse embryos is enhanced in presence of their striatal target cells.

Long-term survival of mesencephalic and striatal cells from mouse embryos in dissociated primary cultures is described. Catecholaminergic neurons in mesencephalic culutres were identified histochemically and by measuring [3H]dopamine uptake and synthesis from [3H]tyrosine. According to experiments using specific inhibitors of catecholamine uptake, at least two-thirds of the catecholaminergic neurons are dopaminergic. These neurons differentiated whether or not striatal target cells were present, but striatal cells stimulated the development of the dopaminergic neurons. [3H]Dopamine uptake was increased by at least 2-fold regardless of the age of the cocultures (4-15 days). Enhanced [3H]dopamine synthesis was also observed (at least 2-fold) at later times (12-15 days).

Animals