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Brachytherapy (BT), especially in high dose rate (HDR), has become increasingly complex owing to the use of image-guided techniques and the introduction of advanced applicators. Consequently, radiotherapy technologists and medical physicists (RTMPs) require substantial training to enhance their knowledge and technical skills in image-guided brachytherapy. However, the current status of the RTMP workload, individual abilities and quality control (QC) of BT units in Japan remains unclear. To address this issue, we conducted a questionnaire survey from June to August 2022 in all 837 radiation treatment facilities in Japan involving RTMPs. This survey focused on gynecological cancers treated with HDR-BT (GY-HDR) and permanent prostate implantation using low-dose-rate BT (PR-LDR). The responses revealed that the average working time in the overall process for HDR varied: 120 min for intracavitary BT and 180 min for intracavitary BT combined with interstitial BT. The QC implementation rate, in accordance with domestic guidelines, was 65% for GY-HDR and 44% for PR-LDR, which was lower than the 69% observed for external beam radiation therapy (EBRT). Additionally, the implementation rate during regular working hours was low. Even among RTMP working in facilities performing BT, the proportion of those able to perform QC for BT units was ~30% for GY-HDR and <20% for PR-LDR, significantly lower than the 80% achieved for EBRT. This study highlights the vulnerabilities of Japan's BT unit QC implementation structure. Addressing these issues requires appropriate training of the RTMP staff to safely perform BT tasks and improvements in practical education and training systems., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth of Lecanicillium primulinum (current name: Flavocillium primulinum) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated as an antifungal active compound from Aspergillus burnettii. However, the antifungal activity of 1 has been revealed in only one fungal species, and the mechanism of action of 1 remains unknown. After the validation of mitochondrial function inhibitory of 1, we envisioned a new antimalarial drug discovery platform based on mitochondrial function inhibitory activity. We evaluated antimalarial activity and 1 showed antimalarial activity against Plasmodium falciparum FCR3 (chloroquine sensitive) and the K1 strain (chloroquine resistant). Our study revealed the utility of our original screening system based on a multidrug-sensitive yeast and mitochondrial function inhibitory activity for the discovery of new antimalarial drug candidates., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

An antifungal polyene-decalin polyketide natural product, burnettiene A ( 1 ) has been re-discovered from the culture broth of Lecanicillium primulinum (current name: Flavocillium primulinum ) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated from Aspergillus burnettii . The antifungal activity of 1 against Candida albicans has been reported. However, only one fungal species for the antifungal activity of 1 has been revealed, and details of the antifungal activity against other pathogenic fungus remain unknown. After extensive screening for antifungal activity, we found that 1 exhibits broad antifungal activity against pathogenic plant fungi, including Colletotrichum gloeosporioides , Botrytis cinerea , Pyricularia oryzae , Leptosphaeria maculans , and Rhizoctonia solani . Furthermore, we synthesized 12 derivatives from 1 and evaluated their antifungal activity to reveal the detailed structure-activity relationship. The methyl ester derivative showed antifungal activity against Saccharomyces cerevisiae 12geneΔ0HSR-iERG6 100-fold more potent than that of 1 . Our research indicates that 1 would be a promising natural product as a new fungicidal candidate and the methyl ester derivative especially has great potential., (© 2024 Pesticide Science Society of Japan.)

We discovered a new tetronomycin analog, C-32-OH tetronomycin (2) from the Streptomyces sp. K20-0247 strain, which produces tetronomycin (1). After NMR analysis of 2, we determined the planar structure. Futhermore, the absolute stereochemistry of 2 was deduced based on the biosynthetic pathway of 1 in the K20-0247 strain and a comparison of experimental electronic circular dichroism (ECD) results of 1 with 2. While 2 exihibits potent antibacterial activity aganist Gram-positive baceria including vancomycin-intermediate Staphylococcus aureus (VISA) strains and vancomycin-resistant Enterococci (VRE), the antibacterial activity of 2 shows 16-32-folds weaker than that of 1 suggesting that the C-34 methyl group in 1 is one of the very important functinal group. Moreover, we evaluated the ionophore activity of 1 and 2 and neither compound shows ionophore activity at reasonable concetrations. Our research suggests that 1 and 2 would have different target(s) from an ionophore mechanism in the antibacterial activity and tetronomycins are promising natural products for broad-spectrum antibiotics., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Luminamicin ( 1 ) isolated in 1985, is a macrodiolide compound exhibiting selective antibacterial activity against anaerobes. However, the antibacterial activity of 1 was not fully examined. In this research, re-evaluation of the antibacterial activity of 1 revealed that 1 is a narrow spectrum and potent antibiotic against Clostridioides difficile ( C. difficile ) and effective against fidaxomicin resistant C. difficile strain. This prompted us to obtain luminamicin resistant C. difficile strains for the determination of the molecular target of 1 in C. difficile . Sequence analysis of 1 -resistant C. difficile indicated that the mode of action of 1 differs from that of fidaxomicin. This is because no mutation was observed in RNA polymerase and mutations were observed in a hypothetical protein and cell wall protein. Furthermore, we synthesized derivatives from 1 to study the structure-activity relationship. This research indicated that the maleic anhydride and the enol ether moieties seem to be pivotal functional groups to maintain the antibacterial activity against C. difficile and the 14-membered lactone may contribute to taking an appropriate molecular conformation.

Tetronomycin ( 1 ), first isolated from a cultured broth of Streptomyces sp. by Juslen et al . in 1974, is a polycyclic polyether compound. However, the biological activity of 1 has not been thoroughly examined. In this study, we found that 1 exhibits more potent antibacterial activity than two well-known antibacterial drugs (vancomycin and linezolid) and is effective against several drug-resistant clinical isolates including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci . Furthermore, we reassigned the 13 C NMR spectra of 1 and performed a preliminary structure-activity relationship study of 1 to synthesize a chemical probe for target identification, which implied different targets based on its ionophore activity., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

This study aims to assess the efficacy and toxicity of definitive radiotherapy for early-stage endometrial carcinoma. The correlation between CT-based dosimetric parameters and clinical outcomes is also evaluated. Between 2002 and 2006, 10 medically inoperable patients with T1-2 endometrial carcinoma were treated with radiotherapy alone. A combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) was used for 9 patients, and one was treated with HDR-ICBT alone. Dose prescription of HDR-ICBT was determined in reference to CT images at brachytherapy, and a total dose of 22-24 Gy in 4 fractions was delivered to the outer perimeter of the uterine corpus. Dose-volume parameters of the gross tumor volume (GTV), clinical target volume (CTV), and organs at risk were assessed retrospectively using the dose-volume histograms derived from the CT image-based treatment planning system. After a median follow-up of 55 months, 9 patients were alive without evidence of recurrence. One patient died from liver cirrhosis 17 months after radiotherapy. Severe acute and late toxicities were not observed in any of the patients. Average minimum dose to 90% of GTV and CTV (D90) was 88.0 and 45.9 Gy(EQD2), respectively. The minimum dose delivered to 2 cc of the most irradiated volumes of the rectum and sigmoid colon (D(2cc)) was 78.9 and 65.9 Gy(EQD2), respectively. These patients developed Grade 1 late complications. In this study, stage I-II endometrial carcinoma was well-controlled locally with minimum late toxicity by radiotherapy alone with HDR-ICBT. 3D image-based brachytherapy may potentially deliver a sufficiently high dose to the whole tumor without significant increase in dose to surrounding normal tissues.