{"title":"Establishment and characterization of novel cancer cachexia-inducing cell line, Aku60GC, of scirrhous gastric cancer.","authors":"Rei Noguchi, Kazuyoshi Yanagihara, Yuki Iino, Teruo Komatsu, Takanori Kubo, Takuya Ono, Julia Osaki, Yuki Adachi, Shuhei Iwata, Yomogi Shiota, Toshio Seyama, Tadashi Kondo","doi":"10.1007/s13577-025-01208-9","DOIUrl":"10.1007/s13577-025-01208-9","url":null,"abstract":"<p><p>Cancer cachexia is a pathological state characterized by severe weight loss, skeletal muscle depletion, and adipose tissue reduction. Cancer cachexia is observed in gastric cancer (GC) with a higher incidence over 80%. Approximately 80% patients with advanced GC including scirrhous gastric cancer (SGC), which has the worst prognosis among all GC, are affected with cachexia. The exact pathophysiology in SGC cancer cachexia remains elusive, and therapeutic approaches for the cancer cachexia have not been established. Patient-derived cancer cachexia models are promising for elucidating the underlying mechanisms of disease progression and developing novel treatments, none of which originate from SGC. Therefore, we established a novel cancer cachexia-inducing cell line, designated Aku60GC, through stepwise selection of a patient-derived SGC cell line, HSC-60. Subcutaneous implantation of the Aku60GC cells into nude mice resulted in weight loss, muscle atrophy, and adipose tissue depletion with high reproducibility, accompanied by elevation of the circulating cytokines IL-8 and IL-18. Compared to parental HSC-60 cells, Aku60GC cells exhibited additional genomic changes, such as AKT2 and CCNE1 gains, a somatic mutation of RUNX1, and accelerated growth. Thus, our results demonstrate that the Aku60GC cell line is a valuable resource for research on cancer cachexia in SGC.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"82"},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment and characterization of NCC-OS2-C1: a novel patient-derived cell line of osteosarcoma.","authors":"Shuhei Iwata, Rei Noguchi, Julia Osaki, Yuki Adachi, Yomogi Shiota, Koichi Ogura, Shogo Nishino, Akihiko Yoshida, Seiji Ohtori, Akira Kawai, Tadashi Kondo","doi":"10.1007/s13577-025-01198-8","DOIUrl":"https://doi.org/10.1007/s13577-025-01198-8","url":null,"abstract":"<p><p>Osteosarcoma is the most common primary bone sarcoma with a bimodal age distribution. Complete surgical resection with neoadjuvant chemotherapy is the standard curative treatment, and no effective therapeutic strategy has been established for metastatic cases, resulting in poor prognosis. Osteosarcoma presents complex and heterogeneous clinical and molecular features, and no molecular-targeted drugs are available. Therefore, effective multidisciplinary treatment strategies are urgently required. Patient-derived cell lines are essential tools in basic and translational oncology. Considering the heterogeneity of the disease, we established a novel cell line, NCC-OS2-C1, using surgically resected tumor tissues from a patient with osteosarcoma. NCC-OS2-C1 cells demonstrated constant proliferation, spheroid formation, and invasion. In addition, we demonstrated that NCC-OS2-C1 is applicable for the high-throughput screening of drugs. Thus, NCC-OS2-C1 is a valuable tool for basic and translational research on osteosarcoma.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"81"},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-03-31DOI: 10.1007/s13577-025-01196-w
Deirdre Duff, Siobhan Gargan, Aideen Long
{"title":"Non-muscle myosin heavy chain IIA regulates cell morphology, stress fibre structure, and cell migration in FLO-1 oesophageal adenocarcinoma cells.","authors":"Deirdre Duff, Siobhan Gargan, Aideen Long","doi":"10.1007/s13577-025-01196-w","DOIUrl":"10.1007/s13577-025-01196-w","url":null,"abstract":"<p><p>The incidence of oesophageal adenocarcinoma (OAC) is increasing at a rapid rate in Western countries. Early oesophageal cancer is often asymptomatic and metastatic disease is common at presentation leading to poor prognosis and survival rates. Cell migration is tightly controlled in the healthy cell but can become dysregulated in diseases such as OAC where increased cell motility and migration can contribute to metastasis. We investigated the role of an actin-based molecular motor, non-muscle myosin heavy chain IIA (NMHCIIA) in the migratory capacity of oesophageal adenocarcinoma cells. Immunofluorescence microscopy and ratiometric imaging demonstrated that NMHCIIA co-localises with F-actin at the leading edge and retracting rear of migrating FLO-1 OAC cells. siRNA-mediated depletion of NMHCIIA from FLO-1 cells altered cell morphology, gave rise to an increased number of stress fibre like structures and reduced FLO-1 cell migration. These findings suggest that NMHCIIA influences FLO-1 cell migration by regulating F-actin dynamics and the actin cytoskeleton, providing insight into the mechanisms of migration employed by OAC cells and identifying NMHCIIA as a potential therapeutic target for this disease.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"80"},"PeriodicalIF":3.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-03-26DOI: 10.1007/s13577-025-01209-8
Jie Liu, Peng Ge, Yalan Luo, Hailong Chen
{"title":"The causal dance: trimethylamine N-oxide, obesity, and acute pancreatitis in pathophysiological harmony.","authors":"Jie Liu, Peng Ge, Yalan Luo, Hailong Chen","doi":"10.1007/s13577-025-01209-8","DOIUrl":"https://doi.org/10.1007/s13577-025-01209-8","url":null,"abstract":"<p><p>Trimethylamine N-oxide (TMAO), a compound generated by the gut microbiota, may be associated with acute pancreatitis (AP). Nonetheless, the exact crosstalk mechanism remains unidentified. This study used Mendelian randomization, bioinformatics methods, and in vitro analyses to assess the causal relationship among eating behavior, TMAO, obesity, and AP. Our findings indicate that high-calorie meals elevate circulating TMAO levels, which is significantly associated with obesity risk. An in-depth examination of the GSE24883 and GSE194331 datasets indicated that TMAO-induced macrophage inflammation might be crucial in the obesity-AP relationship. In vitro studies indicate that TMAO may induce macrophage pyroptosis. Our results suggest that high-calorie meals significantly elevate circulating TMAO levels and that TMAO-induced macrophage pyroptosis affects the causal relationship between obesity and AP.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"79"},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: Curzerenone inactivates the nuclear factor-kappa B signaling to suppress malignancy and immune evasion in cervical cancer by targeting CSNK2B.","authors":"Yangyan Sun, Min Wang, Jing Ling, Qunying Wu, Guorong Han, Junxu Zhou","doi":"10.1007/s13577-025-01202-1","DOIUrl":"https://doi.org/10.1007/s13577-025-01202-1","url":null,"abstract":"","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"77"},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-03-24DOI: 10.1007/s13577-025-01204-z
Junyu Wang, Ying Su, Feng Wang
{"title":"Advances in the study of single-walled carbon nanotubes in ophthalmology.","authors":"Junyu Wang, Ying Su, Feng Wang","doi":"10.1007/s13577-025-01204-z","DOIUrl":"https://doi.org/10.1007/s13577-025-01204-z","url":null,"abstract":"<p><p>With the rapid development of nanotechnology, the application of nanomaterials in the medical field shows unprecedented potential and innovative prospects. In particular, single-walled carbon nanotubes (SWCNTs), due to their unique physicochemical properties such as high surface area, excellent thermal and electrical properties, high surface/volume aspect ratio, and high tensile strength, show great potential for application in biomedical and biotechnological fields. Ophthalmology, as a branch of medicine that requires great precision and innovation, is gradually becoming one of the hotspots for nanotechnology applications. Although the research and application of nanomaterials in ophthalmology have made some progress, the potential of SWCNTs in ophthalmology has not yet been explored. This paper is a comprehensive review of the applications of nanomaterials in ophthalmology, including their use in drug delivery, antimicrobials, imaging, tissue repair, and photodynamic therapy, and further explores the similar roles of SWCNTs in other medical fields, thus speculating on their potentially important value in ophthalmic research.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"76"},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment and characterization of NCC-dCS2-C1: a novel patient-derived cell line of dedifferentiated chondrosarcoma.","authors":"Shuhei Iwata, Takuya Ono, Rei Noguchi, Julia Osaki, Yuki Adachi, Yomogi Shiota, Suguru Fukushima, Shogo Nishino, Akihiko Yoshida, Seiji Ohtori, Akira Kawai, Tadashi Kondo","doi":"10.1007/s13577-025-01207-w","DOIUrl":"https://doi.org/10.1007/s13577-025-01207-w","url":null,"abstract":"<p><p>Dedifferentiated chondrosarcoma (dCS) is a rare, aggressive subtype of chondrosarcoma, characterized by an abrupt transition between a low-grade cartilaginous tumor and high-grade non-cartilaginous sarcoma. Treatment of dedifferentiated chondrosarcoma is limited by its high metastatic potential and poor response to chemotherapy and radiotherapy. Surgical resection remains the primary approach; however, recurrence and distant metastases substantially reduce survival rates. To provide a fundamental research resource, we aimed to establish a novel cell line of dCS. We successfully developed the NCC-dCS2-C1 cell line using surgically resected tumor tissue from a patient with dCS. This cell line harbors an IDH1 mutation (p.R132S) and exhibits complex copy number variants. NCC-dCS2-C1 cells exhibited constant proliferation in monolayer culture, spheroid formation in low-attachment plates, and migration. High-throughput screening of 221 anticancer drugs using NCC-dCS2-C1 identified three candidates, ixazomib, pazopanib, and ponatinib, that demonstrated low IC<sub>50</sub> values, indicating their potential efficacy in treating dCS. We conclude that NCC-dCS2-C1 is a valuable tool for preclinical and basic research on dCS.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"78"},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correlation between levels of clock protein expression and effects on temozolomide-resistant glioblastoma and tumor progression.","authors":"Keng-Liang Kuo, Shu-Jyuan Chang, Aij-Lie Kwan, Chee-Yin Chai","doi":"10.1007/s13577-025-01205-y","DOIUrl":"https://doi.org/10.1007/s13577-025-01205-y","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common malignant intracranial neoplasm. Treatment with surgical resection and concurrent chemoradiotherapy may not achieve satisfactory results in life expectancy. Temozolomide (TMZ) chemoresistance is one of the most common reasons for treatment failure, but the role of the circadian cycle and autophagic pathways in this phenomenon is unknown. This study investigated the relationship between the circadian cycle and autophagic pathways in GBM and its TMZ chemoresistance counterpart. The predictive potential of NR1D1 and MGMT was analyzed by using 631 glioma cases derived from the TCGA GBM dataset. Human GBM cell lines (U-87 MG, GBM 8401) and their TMZ chemoresistance counterparts were used for MGMT, circadian proteins (CLOCK, BMAL1, NR1D1), and LC3B analysis. In addition, immunohistochemical staining for NR1D1 was performed in 78 GBM samples, and the results were analyzed with patients' clinicopathological parameters. Results revealed a decrease in NR1D1 expression in GBM cells which could enhance TMZ chemosensitivity. Different expressions of autophagic markers were also noted in GBM cell lines with and without TMZ chemoresistance, indicating a significant role for NR1D1 in TMZ chemoresistance in the GBM cell line. In addition, higher expression of NR1D1 in tumor samples was correlated with poor prognosis and shorter survival. In conclusion, high levels of NR1D1 not only could predict poor prognosis but it could also be used as a chemosensitizer for TMZ in GBM patients.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"75"},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-03-20DOI: 10.1007/s13577-025-01199-7
John Lenon de Souza Santos, Bruno Diaz Paredes, Corynne Stephanie Ahouefa Adanho, Carolina Kymie Vasques Nonaka, Katia Nunes da Silva, Ian Marinho Santos, Erick Correia Loiola, Viviane Aline Oliveira Silva, Clarissa Araújo Gurgel Rocha, Bruno Solano de Freitas Souza
{"title":"Generation and characterization of human-induced pluripotent stem cell lines from patients with autism spectrum disorder and SCN2A variants.","authors":"John Lenon de Souza Santos, Bruno Diaz Paredes, Corynne Stephanie Ahouefa Adanho, Carolina Kymie Vasques Nonaka, Katia Nunes da Silva, Ian Marinho Santos, Erick Correia Loiola, Viviane Aline Oliveira Silva, Clarissa Araújo Gurgel Rocha, Bruno Solano de Freitas Souza","doi":"10.1007/s13577-025-01199-7","DOIUrl":"https://doi.org/10.1007/s13577-025-01199-7","url":null,"abstract":"<p><p>Autism spectrum disorders (ASD) comprise a group of complex neurodevelopmental disorders that affect communication and social interactions. Over a thousand genes have been associated with ASD, with SCN2A standing out due to its critical role in neuronal function and development. Induced pluripotent stem cells (iPSCs) derived from individuals with ASD have become invaluable in vitro models for investigating the cellular and molecular mechanisms underlying the disorder. In this study, we generated and characterized four iPSC clones from peripheral blood mononuclear cells (PBMCs) of two ASD patients carrying loss-of-function variants in the SCN2A gene. These iPSC lines underwent comprehensive characterization through multiple assays. Reverse transcription polymerase chain reaction (RT-PCR), flow cytometry, and immunofluorescence analyses confirmed the presence of pluripotency markers. An embryoid body formation assay demonstrated their potential to differentiate into the three germ layers. Sequencing analysis confirmed the SCN2A variants, while short tandem repeat (STR) analysis authenticated the cell lines, and karyotype analysis ensured chromosomal integrity. The iPSCs exhibited typical morphologic characteristics, including large nuclei with prominent nucleoli, a high nucleus-to-cytoplasm ratio, densely packed cells, and well-defined borders. These cells maintained pluripotency markers, demonstrated the ability to differentiate into the three germ layers, and showed a normal karyotype. Furthermore, we successfully generated cerebral organoids from these cells. Our study establishes a robust platform for further exploration of the pathophysiological mechanisms of ASD, particularly those involving SCN2A.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"74"},"PeriodicalIF":3.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2025-03-20DOI: 10.1007/s13577-025-01192-0
Zhao Yan, Banjun Ruan, Zheng Zhu, Xiaorui Cao, Zifan Lu
{"title":"Azoramide, a novel regulator, favors adipogenesis against osteogenesis through inhibiting the GLP-1 receptor-PKA-β-catenin pathway.","authors":"Zhao Yan, Banjun Ruan, Zheng Zhu, Xiaorui Cao, Zifan Lu","doi":"10.1007/s13577-025-01192-0","DOIUrl":"10.1007/s13577-025-01192-0","url":null,"abstract":"<p><p>The reciprocal fate decision of mesenchymal stem cells (MSCs) to either bone or adipocytes is determined by Wnt-related signaling and the glucagon-like peptide-1 receptor (GLP-1R). Azoramide, an ER stress alleviator, was reported to have an antidiabetic effect. In this study, we investigated the function of azoramide in regulating the lineage determination of MSCs for either adipogenic or osteogenic differentiation. Microcomputed tomography and histological analysis on bone morphogenetic protein (BMP)2-induced parietal periosteum bone formation assays, C3H10T1/2 and mouse bone marrow MSC-derived bone formation and adipogenesis assays, and specific staining for bone tissue and lipid droplets were used to evaluate the role of azoramide on the lineage determination of MSC differentiation. Cells were harvested for Western blot and quantitative real-time polymerase chain reaction (PCR), and immunofluorescence staining was used to explore the potential mechanism of azoramide for regulating MSC differentiation. Based on MSC-derived bone formation assays both in vivo and in vitro, azoramide treatment displayed a cell fate determining ability in favor of adipogenesis over osteogenesis. Further mechanistic characterizations disclosed that both the GLP-1R agonist peptide exendin-4 (Ex-4) and GLP-1R small interfering (si)RNA abrogated azoramide dual effects. Moreover, cAMP-protein kinase A (PKA)-mediated nuclear β-catenin activity was responsible for the negative function of azoramide on bone formation in favor of adipogenesis. These data provide the first evidence to show that azoramide may serve as an inhibitor against GLP-1R in MSC lineage determination.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"73"},"PeriodicalIF":3.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}