Wiley最新文献

Endocrine therapy following breast-conserving surgery in older women with low-risk, early-stage breast cancer was associated with a greater reduction in health-related quality of life (HRQOL) than radiation therapy according to the interim analysis of the EUROPA trial presented at the San Antonio Breast Cancer Symposium¹ and published in The Lancet Oncology.²

The EUROPA trial is a noninferiority, phase 3 study in which 731 women (with a final accrual target of 926 patients) aged 70 years or older with stage I, luminal A–like breast cancer were randomized to a single-modality treatment with either radiotherapy (n = 365) or endocrine therapy (n = 366). The study compared the effects on HRQOL and ipsilateral breast tumor recurrence. Changes in HRQOL from the baseline to 2 years were assessed with the global health status scale of the 30-item European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire.

Results of the preplanned interim analysis, which included 207 patients (104 received radiotherapy, and 103 received endocrine therapy), showed a significant reduction in HRQOL in the patients treated with endocrine therapy versus radiotherapy.

At 2 years, patients treated with endocrine therapy had a mean change from the baseline in global health status of –9.79 (95% CI, –14.45 to –5.13; p < .0001), whereas the mean change for those treated with radiotherapy was –3.40 (95% CI, –7.82 to 1.03; p = .13). The adjusted mean difference between the treatments was 6.39 (95% CI, 0.14–12.65; p = .04), with radiotherapy favored.

Patients treated with radiotherapy also had less frequent treatment-related adverse events than those treated with endocrine therapy (67% vs. 85%). The most common grade 3–4 adverse events were experienced by patients in the endocrinology group (none in the radiotherapy group) and included arthralgia (7%), pelvic organ prolapse (3%), fatigue/hot flashes/myalgia (2%), and bone pain/fractures (2%). Serious adverse events were similar between the two treatment groups.

The lead author of the study, Icro Meattini, MD, an associate professor in the Department of Experimental and Clinical Biomedical Sciences “M. Serio” at the University of Florence in Italy, says that the study shows that single-modality therapy has promise as a noninferior alternative to endocrine therapy for improved HRQOL.

“These findings highlight the potential for personalized treatment approaches that align with patient preferences, comorbidities, and treatment tolerability,” he says, adding that the findings “could influence shared decision-making and reduce overtreatment in a subset of older patients with favorable tumor biology.”

Although the interim results are encouraging, he says that the trial will continue as planned to ensure a robust data set for the final analysis.

Non-native species may cause cumulative impacts on native communities if their abundance continues to increase through time. This negative effect can reflect on the spatial distribution of native species, especially when native and non-native species are phylogenetically similar. Here, we assessed the spatial co-occurrence between native and non-native fish species using long-term abundance data from six locations in a Brazilian floodplain. We tested whether the co-occurrence of native and non-native species is influenced by non-native species abundance and time since first record, and whether the abundance effect is mediated by the phylogenetic relatedness between native and non-native species. We found that non-native abundance was more influential than the time since first record and co-occurrence between native and non-native species was lower when the non-native abundance was high, regardless of phylogenetic relatedness. The interannual variability in non-native species abundance may overshadow long-term trends in determining the temporal effects of non-native species.

Polaritonic Si Metasurfaces

In article number 2420439, Ming Lun Tseng and co-workers introduce a novel Si metasurface that harnesses interband-transition-induced surface polariton resonances for molecular sensing in the deep ultraviolet (DUV) regime. The design enables strong, deep-subwavelength DUV field enhancement, facilitating biomolecular autofluorescence and double-resonance Raman scattering in 2D materials. (Image illustrated by Hsu-Chan Hsiao).

Bispecific antibodies (bsAbs) bridging CD3 on T-cells to tumor-associated antigens (TAA) on tumor cells can direct T-cell immunity to solid tumors. “Bystander killing”, where T-cell targeting of TAA-positive tumor cells also leads to the eradication of TAA-negative cells, may overcome TAA heterogeneity. While bystander activity of activated, engineered T-cells has been shown to be robust and wide-reaching, spatiotemporal aspects of bsAb-mediated bystander activity are unresolved. Here, we developed a model where breast cancer tumoroids varying in HER2 expression were printed in to extracellular matrix (ECM) scaffolds. We generated (1) mixed tumors containing different ratios of HER2⁺ and HER2⁻ tumor cells, and (2) HER2⁺ and HER2⁻ tumoroids spaced at different distances within the ECM scaffold. Subsequently, tumors were exposed to peripheral blood-derived T-cells in the presence of CD3xHER2 bsAbs. We find that CD3xHER2 bsAb-mediated interaction of resting, nonactivated T-cells with HER2⁺ tumor cells is sufficient (1) to eliminate 50% HER2⁻ cells in mixed tumor areas, and (2) to eradicate distant HER2⁻ tumor areas. Such bystander killing involves paracrine IFNγ and TNFα activity but does not require T-cell accumulation in HER2⁻ areas. These findings indicate that bystander eradication of TAA-negative cells can significantly contribute to bsAb therapy for solid tumors.

Psilocybin, a tryptamine-derived alkaloid, has been granted Breakthrough Therapy designation by the U.S. FDA for treatment-resistant depression, underscoring its clinical importance. Therefore, sustainable and economic production is urgently needed. Manufacturing of psilocybin in Escherichia coli has drawn great attention. However, due to the low expression and activity of the eukaryotic cytochrome P450 enzyme PsiH in the psilocybin biosynthetic pathway, de novo synthesis of psilocybin in prokaryotic cells has been hampered. To overcome this dilemma, we herein demonstrated de novo synthesis of psilocybin in E. coli by constructing PsiH variants with N-terminal domain modifications and expressing the entire biosynthetic pathway at a concordantly low temperature. Improving the supply of precursor and engineering the P450 electron transfer chain resulted in a 33-fold increase in the titre of norbaeocystin (105.3 mg/L), a key intermediate of psilocybin biosynthesis, and a 17-fold increase in the titre of psilocybin (14 mg/L). Further enhancement of psilocybin production was achieved by converting norbaeocystin to psilocybin by overexpressing an extra copy of the methyltransferase gene psiM. Finally, 79.4 mg/L of psilocybin was produced by optimising flask fermentation conditions, a 100-fold improvement over the starting strain. Our work demonstrates the successful fungal P450 engineering to improve the catalytic activity in E. coli and will advance the sustainable production of the important antidepressant psilocybin in prokaryotic microbial cells.