Biomedical subjects

Takashi Yamanaka

Publications and source records attributed to Takashi Yamanaka.

4 recordsLinked to original sources

PubMed2026

Trastuzumab deruxtecan rechallenge in HER2-positive metastatic breast cancer: EN-SEMBLE.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is a key treatment for HER2-positive metastatic breast cancer (mBC); however, data on T-DXd rechallenge remain limited. PATIENTS AND METHODS: This post-hoc subgroup analysis evaluated T-DXd rechallenge in patients with HER2-positive mBC using data from EN-SEMBLE, a nationwide cohort study in Japan (N = 664). RESULTS: Twenty-six patients were included. Median real-world progression-free survival, real-world time to treatment failure, and overall survival were 6.5, 4.9, and 14.2 months, respectively. The objective response rate was 27%. Patients who discontinued initial T-DXd without progressive disease had numerically longer real-world progression-free survival. No interstitial lung disease occurred during rechallenge. CONCLUSION: T-DXd rechallenge may have clinical activity in selected patients with HER2-positive mBC. CLINICAL TRIAL REGISTRATION NUMBER: jRCT1030220506.

Humans↗

PubMed2026

Quality of life with palbociclib plus tamoxifen in hormone receptor-positive, HER2-negative advanced breast cancer: results from PATHWAY, an Asian international, double-blind, randomized phase 3 trial.

BACKGROUND: In the Asian international PATHWAY trial, palbociclib-tamoxifen demonstrated improved progression-free survival compared with placebo-tamoxifen in patients with HR+/HER2- locally advanced or metastatic breast cancer (ABC). This analysis compared quality of life (QoL) between treatment arms. METHODS: Pre/peri or postmenopausal women with HR+/HER2- ABC were randomly assigned 1:1 to receive palbociclib-tamoxifen or placebo-tamoxifen. Patient-reported outcomes were assessed on day 1 of cycles 1 (baseline), 4, and 7, and at the end of treatment (EOT) using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Least-square mean (LSM) changes in scores from baseline were calculated. Kaplan-Meier method was used to calculate time to deterioration (TTD) in the minimally important difference (MID) in the pain subscale. RESULTS: In the comparison between treatment arms, no significant differences were observed in LSM changes in scores from baseline in global QoL (cycle 4: 0.70 [95% confidence interval (CI): -5.00, 6.41]; cycle 7: 2.17 [95% CI: -4.14, 8.48]; EOT: -5.19 [95% CI: -11.64, 1.26]). For both the EORTC QLQ-C30 and QLQ-BR23 functional and symptom subscales, no clinically meaningful differences between treatment arms were found in the LSM changes in scores from baseline. Median TTD in the MID in the pain subscale was 32.5 months (95% CI: 11.7, not estimable) for the palbociclib-tamoxifen arm and 21.2 months (95% CI: 5.5, 43.5) for the placebo-tamoxifen arm (hazard ratio = 0.729 [95% CI: 0.467, 1.138]). CONCLUSIONS: The combination of palbociclib and tamoxifen delayed deterioration in patients' QoL while they experienced reduced risk for disease progression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03423199; study registration date: February 6, 2018.

Humans↗

PubMed2025

Multiple introductions of equine influenza virus into the United Kingdom resulted in widespread outbreaks and lineage replacement.

Influenza A viruses (IAVs) are prime examples of emerging viruses in humans and animals. IAV circulation in domestic animals poses a pandemic risk as it provides new opportunities for zoonotic infections. The recent emergence of H5N1 IAV in cows and subsequent spread over multiple states within the USA, together with reports of spillover infections in humans, cats and mice highlight this issue. The horse is a domestic animal in which an avian-origin IAV lineage has been circulating for >60 years. In 2018/19, a Florida Clade 1 (FC1) virus triggered one of the largest epizootics recorded in the UK, which led to the replacement of the Equine Influenza Virus (EIV) Florida Clade 2 (FC2) lineage that had been circulating in the country since 2003. We integrated geographical, epidemiological, and virus genetic data to determine the virological and ecological factors leading to this epizootic. By combining newly-sequenced EIV complete genomes derived from UK outbreaks with existing genomic and epidemiological information, we reconstructed the nationwide viral spread and analysed the global evolution of EIV. We show that there was a single EIV FC1 introduction from the USA into Europe, and multiple independent virus introductions from Europe to the UK. At the UK level, three English regions (East, West Midlands, and North-West) were the main sources of virus during the epizootic, and the number of affected premises together with the number of horses in the local area were found as key predictors of viral spread within the country. At the global level, phylogeographic analysis evidenced a source-sink model for intercontinental EIV migration, with a source population evolving in the USA and directly or indirectly seeding viral lineages into sink populations in other continents. Our results provide insight on the underlying factors that influence IAV spread in domestic animals.

Animals↗

PubMed2025

Low-temperature embryo incubation suppresses off-target mutagenesis during CRISPR-Cas9 genome editing in medaka (Oryzias latipes) and zebrafish (Danio rerio).

Gene knockout using CRISPR-Cas9 is often employed in research aimed at elucidating gene functions in fish. However, CRISPR-Cas9 sometimes introduces unintended alterations, known as off-target mutations. These mutations can reduce the robustness of data during phenotypic analysis. In this study, we focused on the culture temperature, which is known to significantly influence mutagenesis, and examined whether low-temperature culture after introducing CRISPR-Cas9 into early embryos of medaka and zebrafish suppresses off-target mutations. Continuous incubation of medaka at 16 °C significantly reduced off-target mutation rates compared to those at 28 °C; the drawback is that it decreased the survival rate of medaka embryos. Therefore, low-temperature incubation was limited to early development in both zebrafish and medaka, and then the temperature was increased to 28 °C. Under these conditions, the mutation rates of the three off-target regions in medaka (Off-D, Off-P, and Off-A) significantly decreased, whereas those of the three target regions (DJ-1, p4hb, and avt) were unaffected. Similarly, the mutation rate of the zebrafish target region (ywhaqa) remained high, whereas the off-target (Off-Y1) mutation rate significantly reduced. Furthermore, this method effectively suppressed the germ line transmission of off-target mutations in medaka. This approach is effective to obtain more reliable data from the G0 generation of medaka and zebrafish and may reduce the screening effort required to remove individuals with off-target mutations in the F1 generation.

Animals↗