A Case of High-Grade Neuroendocrine Carcinoma That Improved with Bevacizumab plus Modified FOLFOX6 as the Fourth-Line Chemotherapy

High-grade neuroendocrine carcinoma differs from usual neuroendocrine carcinoma, and its prognosis is dismal. In this case report, a case of high-grade neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as the fourth-line chemotherapy is presented. A 29-year-old male with a huge liver tumor was diagnosed with high-grade neuroendocrine carcinoma originating from the liver. Multiple liver and bone metastases were found one month after surgery. He was treated with three chemotherapy regimens used for the management of small-cell lung cancer with extensive disease. However, none of them could be maintained because of tumor progression. He was then treated with bevacizumab plus modified FOLFOX6 as the fourth-line regimen. Dramatic tumor shrinkage was obtained, and a partial response was achieved. This case suggests that high-grade neuroendocrine carcinoma can be treated with bevacizumab in combination with cytotoxic chemotherapy

Integrated omics unveil the secondary metabolic landscape of a basal dinoflagellate

Abstract: Background: Some dinoflagellates cause harmful algal blooms, releasing toxic secondary metabolites, to the detriment of marine ecosystems and human health. Our understanding of dinoflagellate toxin biosynthesis has been hampered by their unusually large genomes. To overcome this challenge, for the first time, we sequenced the genome, microRNAs, and mRNA isoforms of a basal dinoflagellate, Amphidinium gibbosum, and employed an integrated omics approach to understand its secondary metabolite biosynthesis. Results: We assembled the ~ 6.4-Gb A. gibbosum genome, and by probing decoded dinoflagellate genomes and transcriptomes, we identified the non-ribosomal peptide synthetase adenylation domain as essential for generation of specialized metabolites. Upon starving the cells of phosphate and nitrogen, we observed pronounced shifts in metabolite biosynthesis, suggestive of post-transcriptional regulation by microRNAs. Using Iso-Seq and RNA-seq data, we found that alternative splicing and polycistronic expression generate different transcripts for secondary metabolism. Conclusions: Our genomic findings suggest intricate integration of various metabolic enzymes that function iteratively to synthesize metabolites, providing mechanistic insights into how dinoflagellates synthesize secondary metabolites, depending upon nutrient availability. This study provides insights into toxin production associated with dinoflagellate blooms. The genome of this basal dinoflagellate provides important clues about dinoflagellate evolution and overcomes the large genome size, which has been a challenge previously

Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism.

Low body temperature predicts a poor outcome in patients with heart failure, but the underlying pathological mechanisms and implications are largely unknown. Brown adipose tissue (BAT) was initially characterised as a thermogenic organ, and recent studies have suggested it plays a crucial role in maintaining systemic metabolic health. While these reports suggest a potential link between BAT and heart failure, the potential role of BAT dysfunction in heart failure has not been investigated. Here, we demonstrate that alteration of BAT function contributes to development of heart failure through disorientation in choline metabolism. Thoracic aortic constriction (TAC) or myocardial infarction (MI) reduced the thermogenic capacity of BAT in mice, leading to significant reduction of body temperature with cold exposure. BAT became hypoxic with TAC or MI, and hypoxic stress induced apoptosis of brown adipocytes. Enhancement of BAT function improved thermogenesis and cardiac function in TAC mice. Conversely, systolic function was impaired in a mouse model of genetic BAT dysfunction, in association with a low survival rate after TAC. Metabolomic analysis showed that reduced BAT thermogenesis was associated with elevation of plasma trimethylamine N-oxide (TMAO) levels. Administration of TMAO to mice led to significant reduction of phosphocreatine and ATP levels in cardiac tissue via suppression of mitochondrial complex IV activity. Genetic or pharmacological inhibition of flavin-containing monooxygenase reduced the plasma TMAO level in mice, and improved cardiac dysfunction in animals with left ventricular pressure overload. In patients with dilated cardiomyopathy, body temperature was low along with elevation of plasma choline and TMAO levels. These results suggest that maintenance of BAT homeostasis and reducing TMAO production could be potential next-generation therapies for heart failure.We thank Kaori Yoshida, Keiko Uchiyama, Satomi Kawai, Naomi Hatanaka, Yoko Sawaguchi, Runa Washio, Takako Ichihashi, Nanako Koike, Keiko Uchiyama, Masaaki Nameta (Niigata University), Kaori Igarashi, Kaori Saitoh, Keiko Endo, Hiroko Maki, Ayano Ueno, Maki Ohishi, Sanae Yamanaka, Noriko Kagata (Keio University) for their excellent technical assistance, C. Ronald Kahn (Joslin Diabetes Center and Harvard Medical School) for providing the BAT cell line, Evan Rosen (Harvard Medical School) for providing us Ucp-Cre mice, Kosuke Morikawa (Kyoto University), Tomitake Tsukihara (University of Hyogo) and Shinya Yoshikawa (University of Hyogo) for their professional opinions and suggestions. Tis work was supported by a Grant-in-Aid for Scientifc Research (A) (20H00533) from MEXT, AMED under Grant Numbers JP20ek0210114, and AMED-CREST under Grant Number JP20gm1110012, and Moonshot Research and Development Program (21zf0127003s0201), MEXT Supported Program for the Strategic Research Foundation at Private Universities Japan, Private University Research Branding Project, and Leading Initiative for Excellent Young Researchers, and grants from the Takeda Medical Research Foundation, the Vehicle Racing Commemorative Foundation, Ono Medical Research Foundation, and the Suzuken Memorial Foundation (to T.M.). Support was also provided by a Grants-in-Aid for Young Scientists (Start-up) (26893080), and grants from the Uehara Memorial Foundation, Kowa Life Science Foundation, Manpei Suzuki Diabetes Foundation, SENSHIN Medical Research Foundation, ONO Medical Research Foundation, Tsukada Grant for Niigata University Medical Research, Te Nakajima Foundation, SUZUKEN memorial foundation, HOKUTO Corporation, Mochida Memorial Foundation for Medical & Pharmaceutical Research, Grants-in-Aid for Encouragement of Young Scientists (A) (16H06244), Daiichi Sankyo Foundation of Life Science, AMED Project for Elucidating and Controlling Mechanisms of Aging and Longevity under Grant Number JP17gm5010002, JP18gm5010002, JP19gm5010002, JP20gm5010002, JP21gm5010002, Astellas Foundation for Research on Metabolic Disorders, Research grant from Naito Foundation, Te Japan Geriatrics Society (to I.S.); by a Grant-in-Aid for Scientifc Research (C) (19K08974), Yujin Memorial Grant, Sakakibara Memorial Research Grant from Te Japan Research Promotion Society for Cardiovascular Diseases, TERUMO Life Science Foundation, Kanae Foundation (to Y.Y.), JST ERATO (JPMJER1902), AMED-CREST (JP20gm1010009), the Takeda Science Foundation, the Food Science Institute Foundation (to S.F.), and by a grant from Bourbon (to T.M., I.S. and Y.Y.).S

抗原誘発性Th1・Th2サイトカイン産生に対する性ホルモンの影響の性差

The incidence, severity and prognosis of asthma can be affected by a number of factors, including the patient\u27s age and sex. Clinical observations and epidemiologic studies indicate that the prevalence and severity of asthma is higher among boys than girls, but that the ratio inverts after puberty. The reversal of the male/female prevalence of asthma at puberty strongly suggests a role of sex hormones. However, the mechanisms underlying the gender differences in the prevalence of asthma are not clear. Recently, we suggested that the sex differences were due to those in not only sex hormones but also lymphocyte functions based on findings in a murine model of allergic asthma. Therefore, we investigated the effect of sex hormones on antigen-induced cytokine production by lymphocytes to further investigate these gender differences. Splenocytes from ovalbumin (OVA)-sensitized female mice produced more IL-5, Th2 cytokine, than those from OVA-sensitized male mice, upon simulation with OVA. Progesterone decreased the production of IFN-g, Th1 cytokine, by splenocytes from both sensitized male and female mice. 17β-estradiol had no effect on Th1 and Th2 cytokine production by splenocytes from both mice. However, 5a-dihydrotestosterone decreased the production of Th2 cytokines by splenoytes from sensitized female mice but not these from male mice. Our findings suggest that lymphocytes from males and females have different sensitivities to sex hormones in antigen-induced cytokine production

看護実践力育成のための発展型データベース・シミュレーション教材「Web 聖隷タウン」の開発 : 第1報

報告Reports　本稿は、保健師助産師看護師学校養成所指定規則の一部改正（2022 年４月１日施行）に伴う、本学看護学部のカリキュラム改革推進の一環として、2021 年度より検討が開始された看護実践力育成のための発展型データベース・シミュレーション教材「Web 聖隷タウン」の開発に関する第一報である。本学シミュレーション教育委員会は、「Web 聖隷タウン」の実用に向けた開発として、（１）地域の中の看護視点を育てるためのプロットの開発、（２）Web 聖隷タウン制作の技術的課題解決に向けた実用可能な制作環境の試用および検討を行っている。本稿では、「Web 聖隷タウン」の開発経緯と開発推進のための資源確保について、本教材の持つ機能、これまでの活動経過および今後の課題について報告する

聖隷クリストファー大学看護基礎教育におけるシミュレーション教育の実践

紀要委員会企画Special Articles　本報告では、聖隷クリストファー大学看護基礎教育におけるシミュレーション教育の実践環境の構築、各領域における実践、教育力向上の取り組み、そして課題も含め今後の展望を報告する。本学は米国サミュエルメリット大学と2013 年に大学間交流協定を締結して以来、学生や教員が毎年、研修に赴きシミュレーション教育について学んできた。2016年に看護学部の教員有志によるワーキンググループが結成し、2017 年度より看護学部諮問委員会としてシミュレーション教育委員会が発足した。本学では、看護学部を中心にアクティブラーニングを実践するひとつの手法としてシミュレーション教育を検討し環境構築、研修会など学習の機会の提供、シミュレーションルームの機材および備品管理、シミュレーション教育実施の支援、広報活動など推進してきた。今後、シミュレーション教育を遂行する上で、以下の課題と展望がある。1．教育環境のさらなる充実、2．人員の確保、3．地域の拠点としてのシミュレーション教育の推進、4．活動のための運営資金の獲得である

聖隷クリストファー大学看護基礎教育における2020年度シミュレーション教育の実践報告

紀要委員会企画Special Articles　本報告では、聖隷クリストファー大学看護基礎教育における2020 年度のシミュレーション教育委員会の活動報告および各領域における実践について、以下の内容をふまえ報告する。　①シミュレーション教育の実践環境の構築および学内研修、②コロナ禍における通信設備・運用のテクニカルサポート、③シミュレーション教育の実践（看護学部各領域におけるシミュレーション教育の実践内容）、④看護学部シミュレーション教育ホームページ、⑤本学看護学部のシミュレーション教育に関する国内外の学会発表の実績　今後もシミュレーション教育を推進するための本学の課題である、教育環境のさらなる充実、人員の確保、地域の拠点としてのシミュレーション教育の推進、活動のための運営資金の獲得を目指すべく、近隣施設との連携、研究推進とともに、教員の理解と同意を得ながらさらなる教育環境の整備や教育力の向上のため邁進していく

First occurrence of the hydromedusa Paralovenia bitentaculata (Hydrozoa: Leptomedusae) in Japan

The present note describes a small hydromedusa newly recorded for Japan. Two well-developed specimens of Paralovenia bitentaculata (Hydrozoa: Leptomedusae) were collected at the sea surface in Sasebo city, Nagasaki Prefecture, Kyushu, the southern main island of Japan. Photographs of the preserved specimens are presented

Long-Term Survival in a Patient with Node-Positive Adult-Onset Xp11.2 Translocation Renal Cell Carcinoma

Adult-onset Xp11.2 translocation renal cell carcinoma is a rare malignancy that has an aggressive clinical course and poor prognosis. The reasons for this include the fact that most patients have an advanced clinical stage at diagnosis and also that there is a lack of effective systemic therapy. We herein present the case of a 32-year-old woman suffering from node-positive Xp11.2 translocation renal cell carcinoma, who has undergone radical nephrectomy with an extensive retroperitoneal lymph node dissection, followed by two times of surgical resection for recurrent nodal disease. The patient has experienced no recurrent disease 4.5 years after the last operation and remains free of disease. Surgical approach to recurrent disease, if the recurrent site can be judged to be limited, might be one of the feasible treatment options in patients with Xp11.2 translocation renal cell carcinoma

Follicular dendritic cell sarcoma of small intestine with aberrant T-cell marker expression

Follicular dendritic cell sarcoma (FDCS) is an uncommon neoplasia usually occurring in lymphoid tissue. Herein is present a case of FDCS of the small intestine with positivity for T-cell antigen, simulating T-cell lymphoma. An 82-year-old man consulted a doctor for epigastric pain of one-week duration. Imaging study revealed a mass in the small intestine. Malignant lymphoma was suspected because of high serum levels of soluble interleukin-2 receptor, and resection of the tumor was performed. Microscopically, the tumor was comprised of large pleomorphic cells with reactive small lymphocytes. Most of the nuclei of the tumor cells were round or ovoid-shaped, and some of the tumor cells also showed spindle-shaped nuclei. Although the tumor cells were diffusely positive for CD45RO and CD4 immunohistochemically, negativity for pan-T-cell markers and CD56 were unusual for T-cell lymphoma of intestinal origin. Additional immunohistochemical study demonstrated that the tumor cells were positive for follicular dendritic cell markers including CD23, CD35 and CAN.42, and diagnosis of FDCS was made. To our knowledge, this is the first case of FDCS aberrantly expressing CD45RO, and FDCS expressing T-cell markers can be a pitfall for diagnosis of FDCS