Proceedings of the Japan Academy. Series B, Physical and Biological Sciences最新文献

Rikō Majima published seven papers in this journal, and seeing these papers and their surrounding contexts allows us to glance at the birth of a galaxy of scientists.

Biomedical advances of external-beam radiotherapy (EBRT) with improvements in physical accuracy are reviewed. High-precision (±1 mm) three-dimensional radiotherapy (3DRT) can utilize respective therapeutic open doors in the tumor control probability curve and in the normal tissue complication probability curve instead of the one single therapeutic window in two-dimensional EBRT. High-precision 3DRT achieved higher tumor control and probable survival rates for patients with small peripheral lung and liver cancers. Four-dimensional radiotherapy (4DRT), which can reduce uncertainties in 3DRT due to organ motion by real-time (every 0.1-1 s) tumor-tracking and immediate (0.1-1 s) irradiation, have achieved reduced adverse effects for prostate and pancreatic tumors near the digestive tract and with similar or better tumor control. Particle beam therapy improved tumor control and probable survival for patients with large liver tumors. The clinical outcomes of locally advanced or multiple tumors located near serial-type organs can theoretically be improved further by integrating the 4DRT concept with particle beams.

We launched SCRUM-Japan platform for the cancer genome profiling (CGP) test screening followed by the enrollment to genomically-matched clinical trials in 2015. More than 30,000 tissue-based and 10,000 liquid-based CGP tests have already been performed for enrolling to a total of 127 industry-/investigator-initiated registration trials, which resulted in regulatory approvals of 12 new agents with 14 indications in Japan. Using the clinical-genomic database, a new driver gene was recently discovered with dramatic response by genomically-matched agent. Our comparative study with tissue-based CGPs revealed more usefulness of liquid biopsy in terms of less invasive manner, shorter turn-round time, and higher enrollment rate for matched treatments than tissue-based in gastrointestinal cancers. For detecting minimal/molecular residual disease (MRD) after surgery, post-surgical monitoring with tumor-informed liquid biopsy assay in association with two randomized control trials have also started in 2020 (CIRCULATE-Japan). The observational cohort study showed obvious efficacy of the MRD monitoring for predicting recurrence, leading to change clinical practice in patient selection who should receive adjuvant therapy in the near future.

Studying the central dogma at the single-cell level has gained increasing attention to reveal hidden cell lineages and functions that cannot be studied using traditional bulk analyses. Nonetheless, most single-cell studies exploiting genomic and transcriptomic levels fail to address information on proteins that are central to many important biological processes. Single-cell proteomics enables understanding of the functional status of individual cells and is particularly crucial when the specimen is composed of heterogeneous entities of cells. With the growing importance of this field, significant methodological advancements have emerged recently. These include miniaturized and automated sample preparation, multi-omics analyses, and combined analyses of multiple techniques such as mass spectrometry and microscopy. Moreover, artificial intelligence and single-molecule detection technologies have advanced throughput and improved sensitivity limitations, respectively, over conventional methods. In this review, we summarize cutting-edge methodologies for single-cell proteomics and relevant emerging technologies that have been reported in the last 5 years, and provide an outlook on this research field.

Catalytic asymmetric direct-type aldol reactions of ketones with aldehydes are a perennial puzzle for organic chemists. Notwithstanding the emergence of a myriad of chiral catalysts to address the inherent reversibility of the aldol products, a general method to access acyclic α-chiral ketones from prochiral aryl ketones has remained an unmet synthetic challenge. The approach outlined herein is fundamentally different to that used in conventional catalysis, which typically commences with an α-proton abstraction by a Brønsted base. The use of a chiral 2,2'-bipyridine scandium complex enabled the hydroxymethylation of propiophenone to be run under base-free conditions, which avails effectual suppression of hydrolytic deactivation of the Lewis acid catalyst. Intriguingly, the use of water as a reaction medium had an overriding effect on the progress of the reaction. The sagacious selection of sodium dodecyl sulfate and lithium dodecyl sulfate as surfactants allowed a variety of propiophenone derivatives to react in a highly enantioselective manner.

Micelles are useful and widely applied molecular assemblies, formed from amphiphilic molecules, in water. The majority of amphiphiles possess an alkyl chain as the hydrophobic part. Amphiphiles bearing hydrophilic and hydrophobic polymer chains generate so-called polymeric micelles in water. This review focuses on the recent progress of "aromatic micelles", formed from bent polyaromatic/aromatic amphiphiles, for the development of third-generation micelles. Thanks to multiple host-guest interactions, e.g., the hydrophobic effect and π-π/CH-π interactions, the present micelles display wide-ranging uptake abilities toward various hydrophobic compounds in water. In addition to such host functions, new stimuli-responsive aromatic micelles with pH, light, and redox switches, aromatic oligomer micelles, saccharide-coated aromatic micelles, and related cycloalkane-based micelles were recently developed by our group.

L-DOPA is an amino acid that is used as a treatment for Parkinson's disease. A simple enzymatic synthesis method of L-DOPA had been developed using bacterial L-tyrosine phenol-lyase (Tpl). This review describes research on screening of bacterial strains, culture conditions, properties of the enzyme, reaction mechanism of the enzyme, and the reaction conditions for the production of L-DOPA. Furthermore, molecular bleeding of constitutively Tpl-overproducing strains is described, which were developed based on mutations in a DNA binding protein, TyrR, which controls the induction of tpl gene expression.

Malignant pleural mesothelioma (MPM) is an aggressive tumor of the pleural cavity. Pathologically distinguishing MPM from other pleural lesions is often difficult. We searched for marker antigens to facilitate the pathological diagnosis of MPM and found useful markers for the pathological detection of malignant mesothelioma. Among them, the anti-mesothelioma monoclonal antibody SKM9-2, which was isolated as a clone binding to specimens of MPM (but not to specimens of lung adenocarcinoma) by immunohistochemical screening, showed higher specificity and sensitivity than traditional mesothelioma markers. SKM9-2 recognizes both sialylated O-glycans and peptide sequences in HEG1, and its glycan modifications are specific to mesothelioma. New effective treatments for MPM are needed because the prognosis of patients with MPM is usually poor. SKM9-2 can be used as a seed for next-generation antibody drugs with strong cytotoxic activities. In this review, we have summarized our research on antibody development for MPM diagnosis and treatment.

Gustatory and olfactory receptors receive multiple chemical substances of different types simultaneously, but they can barely discriminate one chemical species from others. In this article, we describe a device used to measure taste, i.e., taste sensors. Toko and colleagues developed a taste sensor equipped with multiarray electrodes using a lipid/polymer membrane as the transducer in 1989. This sensor has a concept of global selectivity to decompose the characteristics of a chemical substance into taste qualities and to quantify them. The use of taste sensors has spread around the world. More than 600 examples of taste-sensing system have been used, while providing the first "taste scale" in the world. This article explains the principle of taste sensors and their application to foods and medicines, and also a novel type of taste sensor using allostery. Taste-sensor technology, the underlying principle of which is different from that of conventional analytical instruments, markedly affects many aspects including social economy as well as the food industry.