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Abstract Glioblastoma multiforme (GBM) is the most common as well as one of the most malignant types of brain cancer. Despite progress in development of novel therapies for the treatment of GBM, it remains largely incurable with a poor prognosis and a very low life expectancy. Recent studies have shown that oleandrin, a unique cardiac glycoside from Nerium oleander, as well as defined extract (PBI-05204) that contains this molecule, inhibit growth of human glioblastoma, and modulate glioblastoma patient-derived stem cell-renewal properties. The present study aimed to investigate the radiosensitization of PBI-05204 in glioblastoma using both in vitro and in vivo cancer models as well as to explore the potential mechanism of actions in GBM. The radiosensitizing effect of PBI-05204 was assessed against human GBM U87MG, U251, T98G and A172 cell lines as well as their relevant xenograft and orthotopic models. The induction of apoptosis, DNA damage and repair of DNA double strand breaks were assessed with determination of caspase 3 and 9 protein expression, DNA laddering, protein expression of rH2AX, Ku70, DNA-PKcs, and RAD51 as well as a Comet Assay. PBI-05204 treatment leads to an increased in vitro sensitivity of GBM cells, including U87MG, U251, T98G and A172 cells, to radiotherapy (RT) in which the main mechanisms are the transition from autophagy to apoptosis and enhanced DNA damage evidenced by increased expression of γH2AX. Additionally, relative increased expression of Ku70, DNA-PKcs and RAD51 due to RT were reduced by PBI-05204 in U87MG and U251 cells, suggesting PBI-05204 lessened RT mediated DNA repair. PBI-05204 significantly enhanced the RT mediated inhibition of tumor growth by 4.7-, 2.1- and 2.2-fold in U87MG, U251 and T98G xenograft models, respectively. The combination of RT and PBI-05204 showed a significantly enhancement of disease-free survival to 103.0 ± 63.2 days compared to the control group (p < 0.001) which was 3-fold longer than that of RT only group. Collectively, these results reveal that PBI-05204 enhances antitumor activity of RT in preclinical/murine models of human GBM. Given the fact that PBI-05204 has already been examined in Phase I and II clinical trials for cancer patients, its efficacy when combined with standard-of-care radiotherapy regimens in GBM should be explored in future clinical trials of this difficult to treat brain cancer. Citation Format: Alessandro Colapietro, Peiying Yang, Alessandra Rosetti, Andrea Mancini, Flora Vital, Stefano Martellucci, Francesco Marampon, Vincenzo Mattei, Giovanni Luca Gravina, Robert Newman, Claudio Festuccia. The botanical drug PBI-05204, a supercritical CO₂ extract of Nerium oleander, augments the antitumor efficacy of radiotherapy in treatment of human glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6307.

Glioblastoma multiforme (GBM) is the most common as well as one of the most malignant types of brain cancer. Despite progress in development of novel therapies for the treatment of GBM, it remains largely incurable with a poor prognosis and a very low life expectancy. Recent studies have shown that oleandrin, a unique cardiac glycoside from Nerium oleander, as well as a defined extract (PBI-05204) that contains this molecule, inhibit growth of human glioblastoma, and modulate glioblastoma patient-derived stem cell-renewal properties. Here we demonstrate that PBI-05204 treatment leads to an increase in vitro in the sensitivity of GBM cells to radiation in which the main mechanisms are the transition from autophagy to apoptosis, enhanced DNA damage and reduced DNA repair after radiotherapy (RT) administration. The combination of PBI-05204 with RT was associated with reduced tumor progression evidenced by both subcutaneous as well as orthotopic implanted GBM tumors. Collectively, these results reveal that PBI-05204 enhances antitumor activity of RT in preclinical/murine models of human GBM. Given the fact that PBI-05204 has already been examined in Phase I and II clinical trials for cancer patients, its efficacy when combined with standard-of-care radiotherapy regimens in GBM should be explored.

Summary: In severely phosphorus (P)‐impoverished environments, plants have evolved to use P very efficiently. Yet, it is unclear how P allocation in leaves contributes to their photosynthetic P‐use efficiency (PPUE) and position along the leaf economics spectrum (LES). We address this question in 10 species of Banksia and Hakea, two highly P‐efficient Proteaceae genera.We characterised traits in leaves of Banksia and Hakea associated with the LES: leaf mass per area, light‐saturated photosynthetic rates, P and nitrogen concentrations, and PPUE. We also determined leaf P partitioning to five biochemical fractions (lipid, nucleic acid, metabolite, inorganic and residual P) and their possible association with the LES.For both genera, PPUE was negatively correlated with fractional allocation of P to lipids, but positively correlated with that to metabolites. For Banksia only, PPUE was negatively correlated with residual P, highlighting a strategy contrasting to that of Hakea. Phosphorus‐allocation patterns significantly explained PPUE but were not linked to the resource acquisition vs resource conservation gradient defined by the LES.We conclude that distinct P‐allocation patterns enable species from different genera to achieve high PPUE and discuss the implications of different P investments. We surmise that different LES axes representing different ecological strategies coexist in extremely P‐impoverished environments. [ABSTRACT FROM AUTHOR]

Genome editing has widespread influence in many fields, including medicine, biotechnology, and agriculture. Despite their origins in chemistry laboratories, these techniques are currently under utilized in chemistry curricula. Introducing future generations of chemists to these emerging technologies is essential in chemistry classrooms. The purpose of this tutorial review is to introduce chemistry audiences--particularly undergraduate chemistry students and educators--to the emerging field of genome editing. Indeed, as the applications of genome editing technologies continue to grow, it will be important for chemistry students to gain a working knowledge of their underlying principles as well as some of their limitations. Here, we aim to provide a general overview of genome editing technologies and highlight some practical ways in which these technologies can be integrated into the undergraduate chemistry curriculum. In the overview, we describe the key players in--and the modes of action of--the three major genome editing technologies, namely, (1) zinc finger nucleases (ZFNs), (2) transcription activator-like effector nucleases (TALENs) and (3) the clustered regularly interspaced short palindromic repeats/CRISPR-associated system (CRISPR/Cas) system. We then highlight several applications of genome editing technologies, particularly the CRISPR/Cas system, and their potential impact on various fields, including basic research, medicine, biotechnology, and the food industry. In this context, we present potential ethical issues associated with the application of genome editing technologies. Finally, by presenting a case study, we highlight the ways that genome editing technologies can be integrated into the undergraduate chemistry curriculum. This review can be added to biochemistry or organic chemistry courses as reading material.

Contribution: An original application of individual rotation to blended learning, which mixes e-learning, discussion groups (seminars), practical laboratory work, and self-motivated tasks called "mini-projects." Background: In examining the changing practices toward students' transferable skills in higher education, current teaching needs to devote much more attention to using multi-modular teaching methods to foster students' key transferable skills, such as logical, analytical, and creative thinking. Intended Outcomes: Rotational blended learning is intended to maximize students' engagement and improve educational outcomes during the learning process. Application Design: A rotated form of existing teaching methods--e-learning, seminars, and group projects--was proposed. A quasi-experimental design, involving classroom observation, student surveys, and overall results, was used with two cohorts of computer system engineering students, one a controlled cohort taught using traditional techniques and the other an experimental cohort taught using a novel rotational blended system. Findings: The influence of blended learning on the subsequent development of critical transferable skills was demonstrated. Results suggest that rotational blended learning is an ideal way to address these challenges, since it allows computer engineering students to reassess and enhance the core skills and competencies they need to acquire in their learning experiences.