Human Cell最新文献

Chondrosarcoma (CS) is a malignant tumor that produces cartilaginous matrix and is the second most common primary bone sarcoma. CS encompasses a range of histological subtypes, with high-grade conventional central CS being particularly rare, occurring at a rate of 1.81 cases per 1 million person-years. Complete surgical resection is the standard curative treatment for this subtype, as radiation therapy and chemotherapy have proven ineffective. High-grade conventional central CS is highly metastatic and prone to recurrence, resulting in a poor prognosis. Therefore, effective multidisciplinary treatment strategies are urgently needed. Patient-derived cell lines offer promising tools for exploring new therapeutic approaches. However, only two cell lines of high-grade CSs are currently available in public cell banks. In this study, we aimed to establish a novel cell line for high-grade conventional central CS. We successfully developed the NCC-CS1-C1 cell line using surgically resected tumor tissues from a patient with conventional central grade 3 CS. This cell line harbored an IDH1 mutation (p.R132S), commonly found in 50% of CS cases, and exhibited complex copy number variants. A high-throughput screening of 221 anti-cancer drugs identified five candidates-bortezomib, carfilzomib, doxorubicin, panobinostat, and romidepsin-that demonstrated low IC50 values, indicating potential efficacy in treating CS. These findings suggest that NCC-CS1-C1 is a valuable tool for both preclinical and basic research on high-grade conventional central CS.

Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a unique subtype of primary liver cancer displaying both hepatocytic and cholangiocytic differentiation. The development of effective treatments for cHCC-CCA remains challenging because of its high heterogeneity and lack of a suitable model system. Using a three-dimensional culture system, we successfully established two novel cHCC-CCA organoid lines from patients undergoing surgical resection for primary liver cancer. cHCC-CCA organoid lines were authenticated by fingerprint analysis, and their morphology, growth kinetics, and anchorage-independent growth were also characterized. Hematoxylin and eosin staining and immunohistochemical analysis showed that the cHCC-CCA organoids preserved the growth pattern, differentiation grade, and phenotypic characteristics of their parental tumors. Whole-exome sequencing demonstrated that patient-derived cHCC-CCA organoid lines retained the genetic alterations identified in their original tumors. Subcutaneous tumors developed in immunodeficient mice after injection of cHCC-CCA organoids. Histologically, the xenografts recapitulated the features of the original cHCC-CCA tumors, harboring both HCC and intrahepatic cholangiocarcinoma components within the same tumor. The establishment of patient-derived cHCC-CCA organoid lines with high tumorigenicity provides a valuable resource for the mechanistic investigation and drug development of this disease.

Extracellular vesicles (EVs) refer to a diverse range of membranous vesicles that are secreted by various cell types, they can be categorized into two primary subgroups: exosomes and microvesicles. Specifically, exosomes constitute a nanosized subset of EVs characterized by their intact lipid bilayer and diameters ranging from 30 to 150 nm. These vesicles play a crucial role in intercellular communication by transporting a diverse array of biomolecules, which act as cargoes for this communication process. Exosomes have demonstrated significant implications in a wide range of biologic processes and pathologic conditions, including immunity, development, cancer, neurodegenerative diseases, and liver diseases. Liver diseases significantly contribute to the global burden of morbidity and mortality, yet their pathogenesis remains complex and effective therapies are relatively scarce. Emerging evidence suggests that exosomes play a modulatory role in the pathogenesis of liver diseases, including viral hepatitis, non-alcoholic steatohepatitis (NASH), and alcoholic hepatitis (AH). These findings bolster our confidence in the potential of exosomes as biomarkers and therapeutic tools for the diagnosis and treatment of liver diseases. In this comprehensive review, we offer a straightforward overview of exosomes and summarize the current understanding of their role in the pathogenesis of liver diseases. This provides a foundation for novel diagnostic and therapeutic approaches in the treatment of liver diseases.

Myxofibrosarcoma (MFS) is one of the most common soft-tissue sarcomas in elderly patients. Owing to the limited efficacy of chemotherapy and radiotherapy, complete resection is the only available curative treatment. Therefore, developing novel therapies for MFS is important to improve clinical outcomes. Herein, a novel MFS cell line, namely SMU-MFS, was established to better understand the biologic characteristics of MFS and develop new therapies. A tissue sample from the surgically resected tumor tissue of a 56-year-old patient with a tumor was subjected to primary culture. The cell line was established and authenticated by assessing the short tandem repeats of DNA microsatellites. The monolayer cultures of SMU-MFS cells exhibited constant growth, spheroid formation, and invasive capacity. Furthermore, the cells exhibited low chemosensitivity to doxorubicin, eribulin, and pazopanib, which are used to inhibit metastatic progression. In addition, of the four mice inoculated with SMU-MFS cells, tumors developed in two mice after 8 weeks. Altogether, the findings of this study suggest that the SMU-MFS cell line can be a useful tool for investigating MFS development and evaluating novel therapeutic agents.

The N6-methyladenine (m6A) modification is the most common modification of messenger RNAs in eukaryotes and has crucial roles in multiple cancers, including bladder cancer (BLCA). This paper aimed to probe the molecular mechanism of zinc-finger CCCH-type containing 13 (ZC3H13)-mediated N6-methyladenine (m6A) modification in BLCA progression via autophagy. Differential expression of ZC3H13 in BLCA was analyzed by the bioinformatics database. ZC3H13 expression in BLCA tissues and cell lines was determined, and malignant behaviors of BLCA cells were examined in vitro and in vivo. ZC3H13 was decreased in BLCA tissues and cell lines relative to adjacent tissues and normal uroepithelial cells. ZC3H13 overexpression restricted BLCA cell growth in vitro and curbed BLCA development in vivo. ZC3H13 promoted the mRNA stability of paraja ring finger 2 (PJA2) through m6A modification, leading to the ubiquitination degradation of the kinase suppressor of Ras 1 (KSR1). Knockdown of PJA2 and overexpression of KSR1 reversed the inhibitory effect of ZC3H13 on BLCA progression. ZC3H13 degraded KSR1 through m6A modification of PJA2, promoted cell autophagy, and repressed BLCA progression. Overall, ZC3H13 promotes the mRNA stability of PJA2 through m6A modification to degrade KSR1, thereby promoting autophagy in BLCA.

Acute myeloid leukemia (AML) is characterized by impaired differentiation of myeloid cells leading to hematopoietic failure. Despite advances, the molecular mechanisms driving AML remain incompletely understood, limiting the identification and targeting of critical vulnerabilities in leukemic cells. Homeobox (HOX) genes, encoding transcription factors essential for myeloid and lymphoid differentiation, are distributed across four clusters: HOXA (chromosome 7), HOXB (chromosome 17), HOXC (chromosome 12), and HOXD (chromosome 2). In addition to protein-coding sequences, HOX clusters encode non-coding RNAs (ncRNAs), which are functional as transcripts and do not translate into proteins. This is the first study wherein we comprehensively reviewed the literature for HOX-embedded ncRNAs, encompassing long non-coding RNAs (lncRNAs), microRNAs, circular RNAs (circRNAs), and piwiRNAs with a role in AML. To date, there is no evidence of circular RNAs and piwi RNAs encoded from the HOX gene clusters. Our review focuses on how leukemic cells harness the regulatory mechanisms of HOX-cluster-derived ncRNAs, (predominantly HOXA and HOXB) to modulate expression of HOX transcription factors facilitating leukemogenesis. HOX ncRNAs either regulate genes on the same chromosome (e.g., lncRNA HOTTIP) or influence expression of genes on different chromosomes (e.g., HOTAIR, HOX10-AS, miR-196b, and miR-10a). We discuss how specific HOX ncRNA networks are leveraged by leukemic cells, presenting an opportunity to explore targeted therapies and address the molecular heterogeneity of AML. Additionally, the aberrant expression of HOX ncRNAs such as HOXB derived ncRNAs in NPM1 mutated AML suggests their potential utility as improved biomarkers and for prognostication of patients with specific molecular aberrations.

Meningiomas are the most frequent brain tumors, typically benign and curable by surgery. However, some patients experience repeated recurrences from residual tumors. To address such cases, the development of novel therapeutic options is crucial. For this purpose, the availability of cell lines that possess the characteristics of benign meningiomas is essential. Here, we established a benign meningioma cell line under 3% O₂ hypoxic conditions without the induction of immortalization genes. This cell line, named TKB-MEN2, has been stably grown for over two years with more than 20 passages. There were no hotspot telomerase reverse transcriptase (TERT) promoter mutations or cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) homozygous deletions, which are genetic features typical of malignant meningiomas. Cultured under hypoxic conditions, this cell line showed fewer characteristics of cellular senescence, such as morphological changes, IL-6 secretion, and lower senescence-associated b-galactosidase activity, compared to the same cell line cultured under 20% O₂ conditions. This immortalized non-transgenic cell line appears to reflect the characteristics of a genuine benign meningioma, potentially allowing the identification of new therapeutic targets and the development of novel therapies for benign meningiomas.

Mesenchymal stem/stromal cells （MSCs） act as a factor in tumor recurrence after drug treatment with their involvement observed in various cancer types. As a constituent of the tumor microenvironment (TME), MSCs not only provide support to tumor growth but also establish connections with diverse cell populations within the TME, serving as mediators linking different tumor-associated components. MSCs play an important role in maintaining tumor progression due to their stem cell properties and remarkable differentiation capacity. Given the intensification of tumor research and the encouraging results achieved in recent years，the aim of this article is to investigate the supportive role of MSCs in tumor cells as well as in various cellular and non-cellular components of the tumor microenvironment. Furthermore, the article shows that MSCs do not have a specific anatomical ecological niche and describes the contribution of MSCs to the maintenance of tumor homeostasis on the basis of homing, plasticity and tumor-forming properties. By elucidating the critical roles of different components of TME, this study provides a comprehensive understanding of tumor therapy and may offer new insights into defeating cancer.

Giant cell tumor of bone (GCTB) is a rare bone tumor that is genetically characterized by a unique mutation in the H3-3A gene. Curative surgical resection is the standard treatment. Unfortunately, a considerable proportion of patients with GCTB have local recurrence and pulmonary metastasis after surgical treatment, and current chemotherapy treatments have shown non-effective. Considering the heterogeneity of the disease, patient-derived cancer models established from multiple cases are required. Therefore, we aimed to establish novel GCTB cell lines for use in preclinical studies. In this study, we successfully established two GCTB cell lines, NCC-GCTB14-C1 and NCC-GCTB15-C1. Both cell lines retained the genetic characteristics of the original tumors, constantly proliferated, and exhibited migratory activity. These cells formed spheroids with morphologically variable phenotypes. We found that they were compatible with chemosensitivity assays, and drug screening using these cell lines led to the identification of potential therapeutic candidates for GCTB. Therefore, NCC-GCTB14-C1 and NCC-GCTB15-C1 may be useful for elucidating the pathogenesis of and developing novel treatments for GCTB.

Stem cells, particularly bulge hair follicle stem cells (HFSCs), have recently attracted significant interest due to their potential for tissue repair and regeneration. These cells, marked by their expression of Nestin (a neural stem cell marker), suggest the possibility of neural differentiation into neurons. This study investigated the use of retinoic acid (RA) and epidermal growth factor (EGF) to induce HFSC transformation into mature neurons, identified by synaptophysin expression. Rat whisker follicles were cultured in a medium suitable for HFSC survival and proliferation. Immunostaining techniques were used to identify HFSCs and assess their differentiation into neural cells. The addition of RA and EGF to the culture medium aimed to induce this differentiation. Findings demonstrate that HFSCs expressed Nestin, indicating their pluripotent nature. Treatment with RA and EGF resulted in synaptophysin expression, a marker of mature neurons, which was absent in the control group. However, this treatment group also displayed a decrease in the expression of other neural markers (βIII tubulin and NeuN). This study suggests that a combination of RA and EGF can accelerate HFSC differentiation into synaptophysin-positive cells in vitro. This research paves the way for further exploration of its potential application in neuro-regeneration.