Biomedical research (Tokyo, Japan)最新文献

A novel 3D immuno-electron microscopy and its application to the Golgi apparatus. 一种新型三维免疫电子显微镜及其在高尔基体上的应用。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.25

Daisuke Koga, Satoshi Kusumi, Hirokazu Yagi, Koichi Kato

{"title":"A novel 3D immuno-electron microscopy and its application to the Golgi apparatus.","authors":"Daisuke Koga, Satoshi Kusumi, Hirokazu Yagi, Koichi Kato","doi":"10.2220/biomedres.47.25","DOIUrl":"10.2220/biomedres.47.25","url":null,"abstract":"Serial section scanning electron microscopy (SEM) is useful for revealing the three-dimensional (3D) architecture of organelles by acquiring backscattered electron images of ultrathin serial sections of resin-embedded tissues on solid substrates. However, comprehensive analyses of organelle function require a combination of ultrastructural and molecular localization data. In the present study, we developed a novel 3D immuno-electron microscopy (immuno-EM) approach that combines Tokuyasu cryosectioning with serial section SEM to elucidate the spatial distribution of organelle-associated proteins. Thick cryosections of tissues were immunolabeled with primary antibodies and FluoroNanogold-conjugated secondary antibodies, followed by gold enhancement, resin embedding, and serial sectioning and SEM. Serial tomographic images of organelles were aligned and segmented to generate 3D reconstructions. To demonstrate the effectiveness of the method, we visualized the localization of GM130, a representative cis-Golgi matrix protein, in a 3D model of the Golgi apparatus in rat pituitary gonadotropes. The 3D model revealed a spherical Golgi apparatus composed of five cisternae arranged in cis-trans order, with GM130 localized on the outer cisternae, consistent with previous findings. Our 3D immuno-EM technique enables the detailed 3D visualization of the Golgi apparatus and other organelles as well as analyses of the spatial distribution of target proteins in their 3D reconstructions.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 1","pages":"25-34"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101229","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

Atomic force microscopy identifies filamentous structures comprising mitotic chromosomes. 原子力显微镜鉴定了包含有丝分裂染色体的丝状结构。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.121

Moeri Suzuki, Motoko Takahashi, Toru Hirota, Osamu Hoshi

{"title":"Atomic force microscopy identifies filamentous structures comprising mitotic chromosomes.","authors":"Moeri Suzuki, Motoko Takahashi, Toru Hirota, Osamu Hoshi","doi":"10.2220/biomedres.47.121","DOIUrl":"10.2220/biomedres.47.121","url":null,"abstract":"Chromosomes undergo dynamic structural reorganization during the cell cycle and become highly condensed during mitosis. This condensation process involves the assembly of chromatin fibers, in which chromosome-associated proteins (e.g., condensin) and post-translational modifications (e.g., histone deacetylation) play key roles. Although an increasing number of studies have advanced our understanding of chromatin fiber assembly into chromosomes, detailed morphological information on chromatids remains limited. In this report, we used atomic force microscopy to examine the nanoscale structure of chromosomes preserved in liquid and found that mitotic chromosomes are composed of a series of thin filamentous structures. Quantitative analysis of chromosomes from the chromokinesin KIF4A-depleted cells and under histone deacetylase inhibition revealed that the filament width and inter-filament spacing are regulated by KIF4A and histone deacetylation, likely reflecting their specific contributions at different hierarchical levels of chromosome assembly. These findings demonstrate that atomic force microscopy enables the detection of fine nanoscale structural alterations beyond the resolution of optical microscopy and provides new morphological insights into the organization of mitotic chromosomes.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 3","pages":"121-129"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148020375","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

Three-dimensional morphological analysis of ghrelin-producing cells in the rat fundic gland by combining serial section scanning electron microscopy and immunogold technique. 结合连续切片扫描电镜和免疫金技术对大鼠基底腺生长素产生细胞的三维形态学分析。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.35

Daisuke Koga, Satoshi Kusumi, Takahiro Sato

{"title":"Three-dimensional morphological analysis of ghrelin-producing cells in the rat fundic gland by combining serial section scanning electron microscopy and immunogold technique.","authors":"Daisuke Koga, Satoshi Kusumi, Takahiro Sato","doi":"10.2220/biomedres.47.35","DOIUrl":"10.2220/biomedres.47.35","url":null,"abstract":"Ghrelin-producing cells (ghrelin cells) in rat fundic glands were analyzed three-dimensionally by combining serial section scanning electron microscopy with immunogold labeling to elucidate their ultrastructural characteristics. This approach enabled unambiguous identification of ghrelin cells and the three-dimensional (3D) reconstruction of their organelles with special reference to primary cilium. Rat ghrelin cells were morphologically classified into two types: ciliated ghrelin cells possessing primary cilia and non-ciliated ghrelin cells. In ciliated cells, primary cilia protruded from basal bodies located near the Golgi apparatus and were largely or entirely enclosed within ciliary pockets. Ghrelin-positive secretory granules were electron-dense and spherical. Ciliated and non-ciliated cells contained both large (250-350 nm) and small (100-200 nm) ghrelin-positive granules. In ciliated cells, the granules were densely accumulated in a localized region of the cytoplasm, being opposite the Golgi apparatus across the nucleus; in non-ciliated cells they were densely distributed throughout the cytoplasm. The ultrastructure of the basement membrane and overall 3D configuration of the Golgi apparatus also differed between the two cell types. Our results provide novel insights into the morphological organization of ghrelin cells, whose 3D ultrastructural features have been unclear in conventional two-dimensional transmission electron microscopy using single ultrathin sections.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 1","pages":"35-46"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101205","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

Habitual exercise prior to intracerebral hemorrhage primes brain environment against injury in a dose-dependent manner of the exercise. 脑出血前的习惯性运动以剂量依赖的方式使脑环境免受损伤。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.103

Yuichiro Oka, Takuya Sugiyama, Ke Chen, Hana Takamura, Yushan Liu, Yuan Ding, Ginjiro Shishido, Hiroshi Maejima

{"title":"Habitual exercise prior to intracerebral hemorrhage primes brain environment against injury in a dose-dependent manner of the exercise.","authors":"Yuichiro Oka, Takuya Sugiyama, Ke Chen, Hana Takamura, Yushan Liu, Yuan Ding, Ginjiro Shishido, Hiroshi Maejima","doi":"10.2220/biomedres.47.103","DOIUrl":"10.2220/biomedres.47.103","url":null,"abstract":"Intracerebral hemorrhage (ICH) is a devastating form of stroke with limited treatment options. Although exercise is beneficial in ischemic stroke, its preconditioning effects in hemorrhagic stroke remain unclear. We examined whether voluntary wheel running prior to ICH modulates acute outcomes and gene expression. Male ICR mice underwent three weeks of voluntary running or sedentary housing before ICH induction. Neurological function was assessed 3 days post-ICH, and perihematomal tissue was analyzed by quantitative PCR. ICH increased expression of Iba1, GFAP, C3, MMP9, TIMP1, and Caspase3, while reducing BDNF expression. Exercise preconditioning did not improve acute behavioral deficits at the group level. However, running distance strongly predicted molecular and pathological responses. BDNF expression correlated positively with exercise volume, whereas C3 showed a negative correlation, with a similar trend for GFAP. Caspase3 and Bax expression were negatively correlated with running distance. Although hematoma volume did not differ significantly between groups, greater running distance was associated with smaller hematoma volume within the exercise group. These findings indicate that habitual voluntary exercise does not attenuate acute functional deficits after ICH but induces dose-dependent molecular adaptations related to neuroplasticity, glial inflammation, and cell death, potentially priming the brain for enhanced recovery in later phases.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 3","pages":"103-112"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148020432","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

Differences in tumor-associated cytokine production and immune mechanisms between myofibroblastic cancer associated fibroblasts and myofibroblasts. 肌成纤维细胞癌相关成纤维细胞和肌成纤维细胞之间肿瘤相关细胞因子产生和免疫机制的差异。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.67

Kosei Kubota, Ken Furudate, Tomoh Matsumiya, Norihiko Narita, Yoshihiro Tamura, Eiji Ikami, Wataru Kobayashi

{"title":"Differences in tumor-associated cytokine production and immune mechanisms between myofibroblastic cancer associated fibroblasts and myofibroblasts.","authors":"Kosei Kubota, Ken Furudate, Tomoh Matsumiya, Norihiko Narita, Yoshihiro Tamura, Eiji Ikami, Wataru Kobayashi","doi":"10.2220/biomedres.47.67","DOIUrl":"10.2220/biomedres.47.67","url":null,"abstract":"Despite advances in oral cancer treatment, therapeutic resistance remains a major challenge. Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the tumor microenvironment. Building on our previous findings on immune responses in gingival fibroblasts, we investigated the immune characteristics of CAFs. Myofibroblast CAF-like cells (myCAF-like) were established using a co-culture system and compared with gingival fibroblast-derived myofibroblasts. MyCAF-like cells exhibited markedly reduced expression of TLR3 and TLR4, whereas RIG-I, COX-2, IL-1β, IL-6, and IL-8 were significantly upregulated. Activation of p38 MAPK signaling contributed to the increased expression of COX-2 and pro-inflammatory cytokines, and TGF-β was involved in the phenotypic transformation of gingival fibroblasts into myCAF-like cells. Microarray analysis revealed upregulation of IL-1α, IL-1β, CXCL8, PTGS2, and CXCL5, alongside downregulation of OMD, COL15A1, and ASPN in myCAF-like cells. Collectively, these findings demonstrate that CAFs acquire a distinct inflammatory signature that differs from gingival fibroblasts and promotes tumor invasion and progression. Targeting CAF-associated inflammatory and signaling pathways may represent a promising strategy to overcome tumor infiltration and treatment resistance in oral cancer.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 2","pages":"67-76"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518001","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

CaMKII promotes BCR-induced apoptosis through Bcl-xL downregulation in immature B cells. CaMKII通过下调Bcl-xL在未成熟B细胞中促进bcr诱导的凋亡。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.131

Ryosuke Okubo, Ryutaro Kajihara

{"title":"CaMKII promotes BCR-induced apoptosis through Bcl-xL downregulation in immature B cells.","authors":"Ryosuke Okubo, Ryutaro Kajihara","doi":"10.2220/biomedres.47.131","DOIUrl":"10.2220/biomedres.47.131","url":null,"abstract":"B cell antigen receptor (BCR) signaling plays a critical role in regulating B cell fate, including activation, tolerance, and apoptosis. In immature B cells, strong BCR engagement induces apoptosis, which contributes to the elimination of autoreactive clones during negative selection. However, the molecular mechanisms linking BCR signaling to apoptotic pathways remain incompletely understood. In this study, we investigated the role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in BCR-induced apoptosis using the immature B cell line WEHI-231. Stimulation of the BCR with anti-IgM antibody induced a rapid increase in intracellular Ca2+ levels and promoted apoptosis in WEHI-231 cells. BCR engagement also induced phosphorylation of CaMKII, indicating activation of this kinase downstream of Ca2+ signaling. Pharmacological inhibition of CaMKII with KN-93, a CaMKII inhibitor, attenuated BCR-induced apoptosis, whereas overexpression of CaMKII enhanced cell death. We further found that BCR stimulation resulted in downregulation of the anti-apoptotic protein Bcl-xL, and inhibition of CaMKII prevented this reduction. Conversely, CaMKII overexpression further enhanced Bcl-xL downregulation following BCR stimulation. Importantly, restoration of Bcl-xL expression significantly rescued CaMKII-mediated apoptosis. These findings identify a Ca2+-CaMKII-Bcl-xL signaling axis that promotes BCR-induced apoptosis in immature B cells.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 3","pages":"131-139"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148020418","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

Tenascin-XB plays a role in the infiltration of immune cells in tumor microenvironment. Tenascin-XB在肿瘤微环境中参与免疫细胞的浸润。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.11

Ao Gong, Yuichi Iida, Kohei Kawakami, Kazuo Yamada, Yasuyuki Saito, Ken-Ichi Matsumoto

{"title":"Tenascin-XB plays a role in the infiltration of immune cells in tumor microenvironment.","authors":"Ao Gong, Yuichi Iida, Kohei Kawakami, Kazuo Yamada, Yasuyuki Saito, Ken-Ichi Matsumoto","doi":"10.2220/biomedres.47.11","DOIUrl":"10.2220/biomedres.47.11","url":null,"abstract":"We previously showed that tenascin-XB (TNXB) contributes to tumor suppressor function. The present study aimed to assess the tumor-suppressive mechanism of TNXB by focusing on immune cell infiltration into the tumor microenvironment (TME). We revealed that B16-OVA melanoma cells (MO5)-bearing TNXB-deficient (Tnxb-/-) mice exhibited significant tumor progression and a poor survival rate. Allogeneic mixed lymphocyte reaction showed reduced numbers and increased activation of both CD4+ and CD8+ T cells from Tnxb-/- spleens. Moreover, T cell activation assay further proved that CD4+ and CD8+ T cells from Tnxb-/- mice were more activated than those from WT mice. RT-qPCR analysis showed that expression of T cell activation-related cytokines and chemokines was significantly decreased in tumor tissues from Tnxb-/- mice. Flow cytometry analysis revealed a reduced infiltration level of CD8+ T cells in both naïve spleens and tumor tissues in Tnxb-/- mice. Ultimately, total activation of CD8+ T cells was decreased in tumor tissues in Tnxb-/- mice. In conclusion, we found that although Tnxb-/- CD4+ and CD8+ T cells tend to be activated more than WT CD4+ and CD8+ T cells, CD8+ T cell infiltration and activation level were attenuated in tumor sites of Tnxb-/- mice.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 1","pages":"11-23"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101268","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

Compressed residual green tea extract prevents capillary regression by inhibiting slow-to-fast muscle fiber transformation in the atrophied skeletal muscle. 压缩残余绿茶提取物通过抑制萎缩骨骼肌中缓慢到快速的肌纤维转化来防止毛细血管退化。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.113

Nao Fujino, Pan Han, Hiroyo Kondo, Jihao Xing, Hao Lin, Noriaki Maeshige, Hidemi Fujino

{"title":"Compressed residual green tea extract prevents capillary regression by inhibiting slow-to-fast muscle fiber transformation in the atrophied skeletal muscle.","authors":"Nao Fujino, Pan Han, Hiroyo Kondo, Jihao Xing, Hao Lin, Noriaki Maeshige, Hidemi Fujino","doi":"10.2220/biomedres.47.113","DOIUrl":"10.2220/biomedres.47.113","url":null,"abstract":"Disuse induces capillary regression in skeletal muscle, which is associated with excessive production of reactive oxygen species (ROS), impaired mitochondrial oxidative capacity, and a shift from slow- to fast-twitch muscle fibers. Green tea is rich in catechins with potent antioxidant properties. We hypothesized that compressed residual green tea extract, a byproduct of green tea manufacturing, may attenuate capillary regression during muscle disuse. Twenty female Wistar rats were randomly assigned to four groups: control (CON), compressed residual green tea supplementation (GTs), hindlimb unloading (HU), and hindlimb unloading with compressed residual green tea supplementation (HU+GTs). Hindlimb unloading was performed for 2 weeks. Compressed residual green tea extract (850 mg/kg/day) or distilled water was administered orally. HU induced significant reductions in soleus muscle mass, capillary-to-fiber (C/F) ratio, slow-twitch fiber proportion, and succinate dehydrogenase (SDH) activity, along with increased ROS production. Compressed residual green tea supplementation significantly attenuated capillary regression, preserved slow fiber composition, restored SDH activity, and suppressed ROS overproduction under unloaded conditions. These findings suggest that compressed residual green tea may serve as a practical nutritional strategy to maintain skeletal muscle capillarity during disuse by preserving oxidative fiber phenotype and mitochondrial function.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 3","pages":"113-120"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148020426","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

Ultrastructural spectrum of oncocytic and chromophobe renal tumors: Insights from osmium maceration-based scanning electron microscopy of formalin-fixed tissues. 嗜癌性和憎色性肾肿瘤的超微结构光谱：福尔马林固定组织基于锇浸渍扫描电镜的观察。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.77

Taro Murakami, Daisuke Koga, Mayuko Akimoto, Hirohisa Okushima, Masayo Kamikokura, Akinori Tada, Kumi Takasawa, Masanori Goto, Masaki Murata, Makoto Osanai, Yoji Nagashima, Yasunari Takakuwa, Akira Takasawa

{"title":"Ultrastructural spectrum of oncocytic and chromophobe renal tumors: Insights from osmium maceration-based scanning electron microscopy of formalin-fixed tissues.","authors":"Taro Murakami, Daisuke Koga, Mayuko Akimoto, Hirohisa Okushima, Masayo Kamikokura, Akinori Tada, Kumi Takasawa, Masanori Goto, Masaki Murata, Makoto Osanai, Yoji Nagashima, Yasunari Takakuwa, Akira Takasawa","doi":"10.2220/biomedres.47.77","DOIUrl":"10.2220/biomedres.47.77","url":null,"abstract":"Ultrastructural analysis has declined in diagnostic pathology since the advent of immunohistochemistry for formalin-fixed paraffin-embedded tissues. To reevaluate the utility of ultrastructural analysis, we adopted the osmium maceration method for scanning electron microscopy (SEM) of formalin-fixed surgical specimens: renal oncocytoma, chromophobe renal cell carcinoma (ChRCC), and tumors categorized as other oncocytic tumors of the kidney (OOT). Light microscopy and immunohistochemistry have revealed that these tumors have overlapping features. SEM observation of the formalin-fixed tumors highlighted distinct morphological features: The oncocytomas contained large mitochondria with vesicular cristae; ChRCCs harbored small mitochondria with microvesicles, and OOTs showed abundant but small mitochondria with lamellar cristae. Quantitative morphometry confirmed that the number of mitochondria in oncocytomas and OOTs exceeded that of non-neoplastic lesions, whereas ChRCCs contained fewer mitochondria. In addition, mitochondria in ChRCCs and OOTs were smaller than those of non-neoplastic lesions, whereas mitochondria in oncocytomas were larger. Thus, SEM of formalin-fixed tissues, optimized by osmium maceration, can provide diagnostically valuable information beyond conventional histology and immunohistochemistry that may help to clarify the biology of challenging oncocytic and chromophobe renal tumors.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 2","pages":"77-87"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518017","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

Poly-(A)-binding protein cytoplasmic 1 gene regulates cell proliferation via TP53 R273H hotspot activation in Japanese patients with common cancer types. Poly-(A)-binding protein cytoplasmic 1基因在日本常见癌症患者中通过TP53 R273H热点激活调控细胞增殖。

Biomedical research (Tokyo, Japan) Pub Date : 2026-01-01 DOI: 10.2220/biomedres.47.191

Shumpei Ohnami, Kouji Maruyama, Takeshi Nagashima, Sumiko Ohnami, Keiichi Hatakeyama, Yuko Watanabe, Keiichi Ohshima, Yu Takahashi, Maki Mizuguchi, Yasuko Sugiyama, Fukumi Kamada, Sou Nakatani, Yuji Shimoda, Kenichi Urakami, Akio Shiomi, Ken Yamaguchi

{"title":"Poly-(A)-binding protein cytoplasmic 1 gene regulates cell proliferation via TP53 R273H hotspot activation in Japanese patients with common cancer types.","authors":"Shumpei Ohnami, Kouji Maruyama, Takeshi Nagashima, Sumiko Ohnami, Keiichi Hatakeyama, Yuko Watanabe, Keiichi Ohshima, Yu Takahashi, Maki Mizuguchi, Yasuko Sugiyama, Fukumi Kamada, Sou Nakatani, Yuji Shimoda, Kenichi Urakami, Akio Shiomi, Ken Yamaguchi","doi":"10.2220/biomedres.47.191","DOIUrl":"10.2220/biomedres.47.191","url":null,"abstract":"Mutations in TP53 occur in approximately half of all common cancer types and play a critical role in tumor progression and metastasis. However, because mutant TP53 can induce both loss- and gain-of-function effects, the development of drugs that directly target TP53 remains challenging. To identify downstream effectors of specific TP53 mutations, we compared gene expression profiles of colorectal (CRC), lung (LC), and stomach cancers (STC) carrying wild-type or mutant TP53. TP53 mutations were frequent (CRC 70.9%, LC 50.1%, STC 45.7%), with TP53-R273H being the most common. Comprehensive analyses comparing patients with TP53 mutations and those with wild-type TP53 identified 24 genes whose expression was significantly increased in TP53-mutated patients, and 20 genes whose expression was decreased across all three tumor types. Among them, PABPC1 showed significantly increased expression in A549 lung cancer cells and MCF7 breast cancer cells with wild-type TP53 transfected with TP53-R273H mutants. Silencing PABPC1 suppressed proliferation of TP53-R273H-mutant colon cancer cells (HT29, SW480). Additionally, patients with CRC harboring the TP53-R273H with high PABPC1 expression had poorer overall survival than those with low PABPC1 expression. These findings indicate that TP53-R273H upregulates PABPC1, suggesting that PABPC1 may function as an oncogene and represent a promising therapeutic target in patients with TP53-R273H mutation.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"47 5","pages":"191-202"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070919","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