Journal of Tokyo Medical University最新文献

巻頭言卷首语

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.198

弘一三宅

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学生支援からメタバースへ从学生支援到麦塔巴斯

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.247

令小川

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PETパラメトリックイメージングが診断の一助となった副腎のchronic expanding hematomaの1例 PET参数成像帮助诊断的肾上腺的chronic expanding hematoma的一个例子

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.263

Nobuhiko Hayashi, Tomonari Kiriyama, Rika Kobayashi, Teppei Nakagomi, Nahiro Yan, Shin-ichiro Kumita, Go Kimura, Yukihiro Kondo

{"title":"PETパラメトリックイメージングが診断の一助となった副腎のchronic expanding hematomaの1例","authors":"Nobuhiko Hayashi, Tomonari Kiriyama, Rika Kobayashi, Teppei Nakagomi, Nahiro Yan, Shin-ichiro Kumita, Go Kimura, Yukihiro Kondo","doi":"10.1272/manms.19.263","DOIUrl":"https://doi.org/10.1272/manms.19.263","url":null,"abstract":"Chronic expanding hematomas (CEH) are hematomas that continue to expand at least one month after onset. CEH often occur in the thoracic cavity or in the extremities secondary to trauma, surgery, anticoagulation therapy, or bleeding disorders. Few studies have reported CEH in retroperitoneal organs such as the adrenal glands and lesions without an apparent etiology. An 80-year-old woman was referred to our hospital for evaluation of a retroperitoneal tumor that was incidentally detected on ultrasonography. Computed tomography and magnetic resonance imaging showed a large left retroperitoneal mass (14 cm in diameter) with gradual peripheral enhancement and a suspected hemorrhagic component within the lesion. Parametric imaging using positron emission tomography (PET) showed mild accumulation of the tracer at the margins of the mass on the conventional standard uptake value images, relatively low accumulation on the slope images, and slightly higher accumulation on intercept images. Postoperative histopathological examination of the resected specimen revealed a mass that was encapsulated with fibrous tissue and primarily consisted of organized clots without evidence of tumor cells; the mass was diagnosed as an idiopathic CEH of the adrenal glands. The margins of the mass showed few inflammatory cell infiltrates consistent with the findings of parametric imaging, which appeared to accurately reflect the dynamics of fluorodeoxyglucose (FDG) in the body. PET parametric imaging can separately assess the metabolism and distribution of FDG in vivo and may be useful to determine the etiology and diagnosis of CEH.","PeriodicalId":35560,"journal":{"name":"Journal of Tokyo Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135989967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of Herpes Simplex Virus-based Vectors for Gene Therapy 单纯疱疹病毒基因治疗载体的研制

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.218

Yoshitaka Miyagawa

{"title":"Development of Herpes Simplex Virus-based Vectors for Gene Therapy","authors":"Yoshitaka Miyagawa","doi":"10.1272/manms.19.218","DOIUrl":"https://doi.org/10.1272/manms.19.218","url":null,"abstract":"In recent years, gene and cell therapies have become widely accepted as new therapeutic modalities, and a number of gene therapy drugs have been approved. Underlying this advance are innovations in gene delivery tools, especially viral vectors, which are no longer simply gene transfer tools in basic research. Since its initial inception, all aspects of gene therapy have been dramatically improved, including their safety, functionality, and production technology. On the other hand, with use of gene therapies clinically, new safety and efficacy concerns have emerged, and gene therapy is now entering a new phase. Both preclinical and clinical data have demonstrated that simple overexpression of a therapeutic gene at a disease site through transduction by a gene delivery vector is not sufficient to ensure safety and therapeutic efficacy. Maturation of this field will require more sophisticated gene delivery vector systems and highly regulated therapeutic gene expression systems to precisely introduce these genes into target cells and express them to the appropriate degree at the appropriate time. Herpes simplex virus (HSV)-based vectors are extremely safe and functional vector systems that have the potential to meet current challenges in gene and cell therapy. This makes HSV vectors promising gene delivery vehicles for gene therapy. This chapter will focus on the current trends in the development of HSV as a delivery vector for gene therapy.","PeriodicalId":35560,"journal":{"name":"Journal of Tokyo Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135989962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene Therapy for Metachromatic Leukodystrophy; MLD 异色性脑白质营养不良的基因治疗MLD

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.224

Noriko Miyake

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悪性黒色腫の薬物治療と問題点恶性黑色素瘤的药物治疗和问题

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.269

俊彦帆足

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Gene Therapy for Hypophosphatasia in Alpl−/− mice (infantile HPP model) -Toward Clinical Application 基因治疗Alpl - / - 小鼠(婴儿HPP模型)-走向临床应用

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.229

Tae Matsumoto

{"title":"Gene Therapy for Hypophosphatasia in Alpl−/− mice (infantile HPP model) -Toward Clinical Application","authors":"Tae Matsumoto","doi":"10.1272/manms.19.229","DOIUrl":"https://doi.org/10.1272/manms.19.229","url":null,"abstract":"Hypophosphatasia (HPP) is an inherited bone disease resulting from a deficiency of tissue-nonspecific alkaline phosphatase (TNALP). It is fatal in its severe perinatal and infantile forms. Asfotase alfa (Strensiq®) is an approved enzyme replacement therapy for HPP. It's use requires injections 3-6 times per week for all of the patient's life. Therefore, although this treatment is effective, it is also burdensome. We investigated the efficacy and safety of a gene therapy drug (TNALP-D10-expressing type 8 adeno-associated virus vector: ARU-2801) administered intramuscularly to Alpl−/− mice (infantile HPP model) and non-human primates with the aim of developing a less burdensome treatment. After administration of 3.0×1011 vg/body (n=4/7) or 1.0×1012 vg/body (n=5/7) ARU-2801, treated mice maintained high plasma ALP activity and exhibited body weight gain and bone maturity similar to wild-type mice throughout their survival period, which was up to 18 months. Biodistribution of ARU-2801 was detected only in the intramuscular region on the administration side. There were no tumors or ectopic calcification detected at autopsy or histopathological examination. After administration of 1.0×1013 vg/body ARU-2801 to juvenile macaque monkeys, durable high plasma ALP levels were sustained for up to 38 weeks with no biochemical abnormalities detected in the blood. Radiological and histopathological examinations also showed no abnormality. The clinical chemistry parameters for ARU-2801-treated mice and macaques indicated that plasma ALP activity is maintained with no toxicities at levels that are potentially clinically efficacious. Thus, ARU-2801, which can be administered as a single dose, has the potential to improve the quality of life of HPP patients by eliminating the need for indefinitely repeated injections.","PeriodicalId":35560,"journal":{"name":"Journal of Tokyo Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135989975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Gene Therapy for Cancer 癌症基因治疗

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.235

Seiji Kuroda, Makoto Sukegawa

{"title":"Gene Therapy for Cancer","authors":"Seiji Kuroda, Makoto Sukegawa","doi":"10.1272/manms.19.235","DOIUrl":"https://doi.org/10.1272/manms.19.235","url":null,"abstract":"A quarter of a century has passed since the expected realization of \"Conquering cancer in the 21st century\" due to advances in pharmaceuticals and medical technology. However, the effectiveness of treatments for malignant tumors, especially refractory cancers, remains inadequate and is difficult to achieve with conventional treatment methods alone. For example, there are high rates of metastasis and residual recurrence following surgical treatment, while chemotherapy and radiotherapy all too quickly lead to disease resistance, and their side effects significantly reduce patients’ quality of life. Under such circumstances, gene therapy products targeting cancer are some of the most highly desired therapies worldwide. The advantages of these innovative treatments are their clear mechanism of action and clinical efficacy based on molecular pathology. Several gene therapies have been approved for hematologic tumors and have shown dramatic therapeutic effects. On the other hand, the efficacy of gene therapies against solid tumors remains limited and improving their therapeutic efficacy remains a major challenge. In this review, we report the background and current status of gene therapy for cancer. In addition, oncolytic virus therapy and CAR-T cell therapy, which have the potential to be curative and are undergoing research and development, will be introduced in detail.","PeriodicalId":35560,"journal":{"name":"Journal of Tokyo Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135989964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Gene Therapy for Ophthalmic Diseases 眼科疾病的基因治疗

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.242

Tsutomu Igarashi

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わが国における胃癌に対する低侵襲手術の現況我国胃癌微创手术现状

Journal of Tokyo Medical University Pub Date : 2023-08-31 DOI: 10.1272/manms.19.254

Nobuyuki Sakurazawa

{"title":"わが国における胃癌に対する低侵襲手術の現況","authors":"Nobuyuki Sakurazawa","doi":"10.1272/manms.19.254","DOIUrl":"https://doi.org/10.1272/manms.19.254","url":null,"abstract":"Gastric cancer used to be the leading cause of cancer mortality in Japan, but the rate has been decreasing in recent years due to declining numbers of Helicobacter pylori infections. However, even now, it is still a major cancer in this country, ranking third in both the number of cases (2019) and number of deaths (2020). Treatment in the preoperative stages has improved thanks to the increased accuracy of preoperative examinations such as endoscopy and computed tomography, with treatment decisions based on prognosis in consideration of the stage of the disease, and the degree of invasiveness the patient will be able to tolerate. Endoscopic resection is indicated for mucosal cancer without lymph node metastasis (stage IA), while anticancer agents are used for stage IV patients with peritoneal dissemination and other cases where radical resection is impossible. Otherwise, surgery is the main treatment. In the past, open surgery dominated, but in recent years, minimally invasive laparoscopic surgery that creates smaller wounds has become widespread. Recently, robotic surgery with such functions as camera shake prevention has been developed, and this enables even more precise surgery. With reference to our own research, this article outlines the historical evolution of gastric cancer surgery and the current status of minimally invasive surgery.","PeriodicalId":35560,"journal":{"name":"Journal of Tokyo Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135989968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0