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http://hdl.handle.net/10564/2594 Sat, 18 May 2024 02:25:54 GMT 2024-05-18T02:25:54Z http://hdl.handle.net/10564/4338 タイトル: High-quality single-cell transcriptomics from ovarian histological sections during folliculogenesis 著者: Ikeda, Hiroki; Miyao, Shintaro; Nagaoka, So; Takashima, Tomoya; Sze-Ming, Law; Yamamoto, Takuya; Kurimoto, Kazuki 抄録: High-quality, straightforward single-cell RNA sequencing (RNA-seq) with spatial resolution remains challenging. Here, we developed DRaqL (direct RNA recovery and quenching for laser capture microdissection), an experimental approach for efficient cell lysis of tissue sections, directly applicable to cDNA amplification. Single-cell RNA-seq combined with DRaqL allowed transcriptomic profiling from alcohol-fixed sections with efficiency comparable with that of profiling from freshly dissociated cells, together with effective exon-exon junction profiling. The combination of DRaqL with protease treatment enabled robust and efficient single-cell transcriptome analysis from formalin-fixed tissue sections. Applying this method to mouse ovarian sections, we were able to predict the transcriptome of oocytes by their size and identified an anomaly in the size-transcriptome relationship relevant to growth retardation of oocytes, in addition to detecting oocyte-specific splice isoforms. Furthermore, we identified differentially expressed genes in granulosa cells in association with their proximity to the oocytes, suggesting distinct epigenetic regulations and cell-cycle activities governing the germ-soma relationship. Thus, DRaqL is a versatile, efficient approach for high-quality single-cell RNA-seq from tissue sections, thereby revealing histological heterogeneity in folliculogenic transcriptome. Sun, 17 Sep 2023 15:00:00 GMT http://hdl.handle.net/10564/4338 2023-09-17T15:00:00Z http://hdl.handle.net/10564/4244 タイトル: 「症例報告」OPSOCLONUS-MYOCLONUS-ATAXIA SYNDROME AFTER ADRENOCORTICOTROPIC HORMONE THERAPY FOR INFANTILE SPASMS IN A BOY WITH DOWN SYNDROME 著者: OHARA, AYAKA; SAKAKIBARA, TAKAFUMI; TAKEDA, YOKO; INAGAKI, ATSUSHI; NOGAMI, KENJI 抄録: Introduction: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare acquired autoimmune paraneoplastic movement disorder associated with neuroblastoma. Additionally, autoimmune diseases and infantile spasms are common comorbidities of Down syndrome (DS). Case report: A boy aged 1 year and 9 months with DS suffered from anti-seizure drug-resistant infantile spasms. We administered low-dose adrenocorticotropic hormone (ACTH; 0.0125 mg/kg/day) for 14 days, and the infantile spasms disappeared; however, he presented with limb myoclonus and involuntary conjugate multidirectional saccadic eye movements on day 3 after the end of ACTH therapy. OMAS was suspected and a complete workup was performed. No tumors, including neuroblastoma, were detected. Antibodies against glutamic acid decarboxylase 65 and Tr/Delta/Notch-like epidermal growth factor-related receptor were found. Two courses of intravenous methylprednisolone pulse therapy (30 mg/kg/day for three consecutive days), oral prednisolone (PSL) treatment (2 mg/kg/day for four consecutive days), and intravenous immunoglobulin treatment (2g/ kg/ 3days) were administered. OMAS symptoms resolved, and PSL tapering was initiated on day 17 after the start of immunomodulatory therapy. Conclusion: We present the case of a patient with DS who developed OMAS after ACTH therapy for infantile spasms. Paraneoplastic syndrome-associated antibody testing facilitated the early diagnosis of OMAS. The development of autoimmune diseases should be considered when ACTH therapy is used for DS. Wed, 30 Aug 2023 15:00:00 GMT http://hdl.handle.net/10564/4244 2023-08-30T15:00:00Z http://hdl.handle.net/10564/4243 タイトル: がん治療におけるクローデイン-4の標的化 著者: 谷, 里奈; 國安, 弘基 抄録: The overexpression of claudin-4 (CLDN4) in many cancers has drawn attention to this protein as a new molecular target. There have been a number of attempts to target CLDN4 for cancer therapy. Targeting of CLDN4 is expected to provide multi-layered effects by enabling direct attacks on CLDN4-overexpressing cancer cells, disrupting the intratumoral microenvironment, and facilitating drug delivery by impairing tight junctions. This article describes anti-CLDN4 antibodies, CLDN4 gene knockdown, CPE and C-CPE, and CLDN4 binding peptides and their potential for cancer therapy. Wed, 30 Aug 2023 15:00:00 GMT http://hdl.handle.net/10564/4243 2023-08-30T15:00:00Z http://hdl.handle.net/10564/4242 タイトル: 「総説」非タイトジャンクション・クローデイン-4の機能 著者: 谷, 里奈; 國安, 弘基 抄録: Claudin-4 (CLDN4) is a key component of tight junctions (TJs) in epithelial cells. CLDN4 is over-expressed in many epithelial malignancies and correlates with cancer progression. Changes in CLDN4 expression have been associated with epigenetic factors (such as hypomethylation of promoterD NA),i nflammation associated with infection and cytokines, and growth factor signaling. CLDN4 helps to maintain the tumor microenvironment by forming TJs and acting as a bar rier to the entry of anticancer drugs into tumors. Decreased expression of CLDN4 is a potential marker of epithelial-mesenchymal transition (EMT), and decreased epithelial differentiation due to reduced CLDN4 activity is involved in EMT induction. Non-TJ CLDN4 also activates integrin beta 1 and YAP to promote proliferation, EMT, and stemness. These roles in cancer have led to investigations of molecular therapies targeting CLDN4 using anti-CLDN4 extracellular domain anti-bodies. gene knockdown. Clostridium perfringens enterotoxin (CPE). and the C-terminus domain of CPE (C-CPE), which have demonstrated the experimental efficacy of this approach. CLDN4 is strongly involved in promoting malignant phenotypes in many epithelial cancers and is regarded as a promising molecular therapeutic target. Wed, 30 Aug 2023 15:00:00 GMT http://hdl.handle.net/10564/4242 2023-08-30T15:00:00Z

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