Efficacy and safety of preoperative chemoradiotherapy with S-1 for advanced rectal cancer: a phase II study

Background: Preoperative chemoradiotherapy (CRT) for patients with rectal cancer is not yet established in Japan. We aimed to evaluate the efficacy and safety of preoperative CRT with S-1, a fixed-dose combination of tegafur, gimeracil, and oteracil potassium. Materials and methods: We conducted a prospective, interventional, non-randomized single-center study. Radiotherapy was administered at a total dose of 45 Gy (1.8 Gy in 25 fractions) for five weeks. S-1 was administered orally for nine weeks (five weeks during and four weeks after radiotherapy) at a dose of 80 mg/m2/day. The endpoint was the pathological complete response (pCR) rate. Results: Twenty-eight patients were finally enrolled. The following patient characteristics were recorded: clinical Stage (II: n = 12, III: n = 16), median age (66 years, range 40–77 years), male/female ratio (20/8), and lesion site (Ra-Rb:3/Rb:23/Rb-P:2). Preoperative treatment was completed in 27 patients (96%). Treatment abandonment occurred because of diarrhea. Grade 3 or higher adverse events were observed in one (4%) patient with two events. No serious adverse events occurred in the ≥ 70 years group. The response rate was 68% in all patients and 68% among elderly patients. Radical resection was achieved in all patients, including 19 (68%) who underwent sphincter-preserving surgery. The pCR rate was 11% (three patients). The five-year disease-free survival rate was 68%, and the overall survival rate was 82%. Local recurrence occurred in only one patient five years after surgery. Conclusion: Preoperative CRT with S-1 alone may be a safe and acceptable regimen from the perspective of adverse events and oncological outcomes. Trial registration: UMIN Clinical Trial Registry: UMIN000013598.  Registered 1 April 2014, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R00001588

Impact estimation of Southern Ocean acidification on calcium carbonate phytoplankton (haptophytes)

第3回極域科学シンポジウム　横断セッション「南極海季節的海氷域における生物地球化学」11月26日（月） 統計数理研究所 セミナー

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

<所内学術研究成果報告>H. 「環境保全・地球環境温暖化防止をターゲットとする新パルプ資源ケナフの栽培と利用に関する研究」

本研究は, エコマテリアルとしての非木材繊維資源に最も適切である一年生植物ケナフ(Hibiscus cannabinus L.)の栽培とその利用を目的に, 1993年より開始した研究である。従来の成果は, すでに本年報1992,\u2794,\u2795,\u2796,\u2797,\u2798,および\u2799年に報告した。特に従来のケナフ栽培の成果の総決算として, 1998年より平塚市および平塚ケナフ普及協会との共同研究が行われてきた。特に, 平塚市では休耕田対策としてケナフの栽培を推奨し, 現在, 栽培したケナフのパルプ化と紙製造を行って市政に還元している。この現状はさらに展開し, 平塚市のみならず日本全国にその輪が広がり大きな活動となっている。これらの栽培や利用は最も基礎的な指導と, より学術的な研究成果の提供が常に必要であり, この点を最も重要な課題としている。さらに, 環境教育に対する展開を学校, 公民館などを中心に行い, 2000年度は, 平塚キャンパスで市内6小学校の生徒28名のケナフ教育を行った。まお, 研究室内では, 栽培研究の他に, a)種子の発芽阻害実験, b)海水による阻害実験, c)生長に伴うクロロフィル量および水分量の測定実験, d)光合成測定実験, e)花の成分(色素)研究, f)葉など各器官の成分研究などを行っている。取り扱った種類も, ローゼル(H. sabdariffa L.)類も加えると30種に近い