PMCID string | Title string | Sentences string |
|---|---|---|
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | This study confirmed circAPP as a gene modifier of miR-6838-5p. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | miR-6838-5p is involved in a series of biological processes in cancer. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | miR-6838-5p is downregulated in osteosarcoma, and induction of miR-6838-5p suppresses tumor metastasis. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | In addition, miR-6838-5p is also involved in myocardial ischemia-reperfusion injury and cerebral hemorrhage injury. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Here, this study implied that miR-6838-5p was lowly expressed in both GIST, and suppression of miR-838-5p mitigated the effect of silencing circAPP. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | This study further showed that, mechanistically, CDV3 was a target of miR-6838-5p. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | CDV3 was documented as an unidentified gene in breast cancer in 1999 and it is overexpressed in hepatocellular carcinoma. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | This study also observed the abundance of CDV3 in GIST, and inhibition of CDV3 impaired circAPP restoration-mediated influences on GIST cell proliferation and the Warburg effect. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Although this study has partially elucidated the function of circAPP in GIST, further research is required in order to develop effective GIST treatments. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | On the one hand, due to the insufficient sample size, the correlation of circAPP with pathological T-staging and poor prognosis of GIST patients has not been established. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | On the other hand, the expression of most circRNAs is significantly correlated with GIST tumor size, mitotic number, and malignant degree by constructing circDNA expression profiles, and does not correlate with tumor site, but no experiments have been performed to verify this idea. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The exact role of this still needs to be further explored, and the molecular expression of the circAPP/miR-6838-5p/CDV3 axis and whether its mechanism is affected by differences in primary sites is a direction for our future in-depth research. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Despite its important role, miR-6838-5p is not the only target regulated by circAPP. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Whether other miRNAs are involved in circAPP affecting Warburg effect of GIST and the related specific mechanism still needs to be further explored. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | This study demonstrates that a novel circRNA, circAPP, is upregulated in GIST tissues and cells and that upregulating circAPP expression promotes the Warburg effect by targeting the miR-6838-5p/CDV3 axis, which is of great significance for the malignant proliferation and metastasis of GIST. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The results provide important data support for the future clinical treatment of GIST and the development of targeted drugs. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Written informed consent for publication was obtained from all participants. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | All subjects were approved by the Affiliated Hospital of Inner Mongolia Minzu University (n° 201211Y62). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Written informed consent was obtained from each subject. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The animal experiments were complied with the ARRIVE guidelines and performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The experiments were approved by the Institutional Animal Care and Use Committee of the Affiliated Hospital of Inner Mongolia Minzu University (n° 201306YT2). |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | GeTu ZhaoRi and ChunJuan Wang designed the research study. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | XianJing Zeng and JinHua Yuan performed the research. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | GeTu ZhaoRi and XianJing Zeng provided help and advice. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | ChunJuan Wang and JinHua Yuan analyzed the data. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | GeTu ZhaoRi and ChunJuan Wang wrote the manuscript. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | JinHua Yuan reviewed and edited the manuscript. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | All authors contributed to editorial changes in the manuscript. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | All authors read and approved the final manuscript. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | Not applicable. |
PMC11269792 | CircRNA amyloid precursor protein by competitive adsorption of microRNA-6838-5p mediates CDV3 expression to enhance malignant behavior and Warburg effect in Gastrointestinal Stromal Tumor | The authors declare no conflicts of interest. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Visceral sarcomas are a rare malignant subgroup of soft tissue sarcomas (STSs). |
PMC10669128 | Preclinical Models of Visceral Sarcomas | STSs, accounting for 1% of all adult tumors, are derived from mesenchymal tissues and exhibit a wide heterogeneity. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Their rarity and the high number of histotypes hinder the understanding of tumor development mechanisms and negatively influence clinical outcomes and treatment approaches. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Although some STSs (~20%) have identifiable genetic markers, as specific mutations or translocations, most are characterized by complex genomic profiles. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Thus, identification of new therapeutic targets and development of personalized therapies are urgent clinical needs. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Although cell lines are useful for preclinical investigations, more reliable preclinical models are required to develop and test new potential therapies. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Here, we provide an overview of the available in vitro and in vivo models of visceral sarcomas, whose gene signatures are still not well characterized, to highlight current challenges and provide insights for future studies. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Visceral sarcomas are rare malignancies belonging to soft tissue sarcomas (STSs). |
PMC10669128 | Preclinical Models of Visceral Sarcomas | STSs are aggressive tumors which arise from the malignant transformation of mesenchymal cells and comprise very heterogeneous entities, accounting for ~1% of all adult human malignancies . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Visceral sarcomas mainly occur in adults and include several histotypes, including liposarcoma (LPS) and angiosarcoma (AS), as well as some leiomyosarcomas (LMSs) and undifferentiated pleomorphic sarcomas (UPSs). |
PMC10669128 | Preclinical Models of Visceral Sarcomas | The most common type of visceral sarcoma is the gastrointestinal stromal tumor (GIST), which arises from the muscle wall of the digestive tract . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | All these neoplasms are believed to derive from the transformation of a common multipotent cell of origin, which can differentiate into specific lineages . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | The precise mechanisms associated with sarcoma development remain to be clarified because of the rarity of the disease and the large number of subtypes . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Indeed, STSs comprise over 70 different histotypes, each characterized by a distinct morphology and molecular aberrations, which usually correspond to a specific clinical course and to specific therapeutic approaches . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Only a small percentage of tumors (~20%) displays distinct diagnostic markers: recurrent genetic alterations, such as specific mutations (e.g., KIT activating mutation in gastrointestinal stromal tumors) and chromosomal translocations (observed in approximately 20% of STSs), or complex genomic profiles and mutated tumor suppressor genes, including TP53 and retinoblastoma 1 (RB1) . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | However, the majority of STSs have nonspecific genetic alteration with a complex karyotype . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Despite their heterogeneity, the first-line treatment for most sarcoma subtypes is still limited to traditional surgery, with or without adjuvant or neoadjuvant radiotherapy, and represents the most common treatment for localized sarcomas. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Unfortunately, most patients develop metastasis, which is treated with chemotherapy, principally doxorubicin and ifosfamide, two main active agents reaching a response rate higher than 20% in advanced STSs . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Nonetheless, the high degree of heterogeneity combined with the poor knowledge of tumor molecular drivers limits treatment efficacy, especially in the case of unresectable, recurrent, or metastatic disease. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Moreover, due to the prevalence of many molecular aberrations within specific sarcomas, few STSs are therapeutically targeted with a 5-year survival rate of ~50% and <10% for localized and metastatic STSs, respectively . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Thus, the identification of new genomic and molecular therapeutic targets and preclinical testing of personalized therapies remain urgent unmet medical needs, especially for visceral sarcomas. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | However, this requires the development of reliable and predictive tumor models to test only the most promising therapies in clinical trials. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | To date, the most used preclinical models in the field include genetically engineered or transgenic mice, xenografts, and PDXs (patient-derived xenografts) . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | However, these models present significant limitations, including high management costs, lengthy experimental processes, and the variable adherence of the animal model to human pathology. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | In this regard, given the rarity of visceral sarcomas, several studies focus on the most common STSs, mainly skeletal sarcomas. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Thus, in this review, we aim to provide an overview of the current in vitro and in vivo models developed for visceral sarcomas, to highlight related challenges and offer insights for forthcoming research. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Historically, cell models have been the primary research tool for the study of STSs, providing valuable insights into sarcoma biology, such as tumor progression and metastasis. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Nonetheless, cancer cell lines present several limitations. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | For instance, prolonged cell culture can determine the onset of secondary genetic changes, including copy number variations and transcriptomic drifts, or specific clone selection, leading to biased results. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Additionally, the research findings suggest that tumor cell lines are more similar to one other than to the original clinical samples, which explains their limited utility. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | In fact, the in vitro and in vivo drug response of certain cell lines was not frequently recapitulated in numerous clinical trials . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Many sarcoma cell lines have been established over the years. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | However, several histological subtypes are largely underrepresented and only a few well-characterized cell lines are publicly available; moreover, many of them are not fully representative of the corresponding tumor tissue . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Hattori and colleagues investigated the current status of the reported sarcoma cell lines, observing that only 139 out of 819 sarcoma cell lines, named according to the WHO classification, have been deposited into public cell banks. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | They also observed that among the 189 histotypes listed in the WHO classification, only 45 have corresponding cell lines . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Thus, an increased number of cell lines representing numerous sarcoma histological subtypes is necessary to effectively understand the complexity of the disease and enhance the utility of tumor cell cultures in cancer research. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Table 1 shows some examples of the available human cell lines derived from different sarcomas. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | In vitro studies with these cell lines have been fundamental in sarcoma research, mainly for drug screening, but also for a better comprehension of the mechanisms behind tumor progression and metastasis . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | An excellent example of successful translational research is represented by the human GIST cell lines widely employed to predict the role of c-KIT signaling and to evaluate the efficiency of imatinib (IM) as a new targeted therapy. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Different KIT mutations affect the apoptotic signal transduction caused by imatinib in GISTs, as observed by Noma and colleagues in the GIST-T1 and the GIST882 lines, carrying activating mutant KIT. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | However, development of imatinib resistance is frequent, and understanding the underlying mechanisms of this event is crucial to establish new treatment strategies . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Thus, alternative approaches have been proposed, such as the inhibition of KIT-dependent signaling pathways or their indirect inhibition by using HSP90 inhibitors (HSP90i). |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Preclinical studies on tumor cell lines have extensively investigated small-molecule HSP90i, which appears to be a promising strategy to overcome imatinib resistance . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Some inhibitors are currently undergoing phase II/III clinical trials in cancer patients, either as standalone treatments or in combination with traditional chemotherapy . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | The effects of new classes of anti-cancer agents involved in epigenetic and non-epigenetic regulation, alone or in combination with other anti-cancer therapies, are widely investigated in tumor cell lines . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | In this regard, Mühlenberg’s group observed that the histone deacetylase (HDAC) inhibitors (HDACi) SAHA and panobinostat (LBH589) hinder cell growth in KIT-positive (GIST-T1, GIST822, and GIST48) but not in KIT-negative cells (GIST62, GIST48B, and GIST522). |
PMC10669128 | Preclinical Models of Visceral Sarcomas | This proves that HDACi primarily act by targeting the oncogenic KIT and exert their strong antiproliferative and proapoptotic effects in both IM-sensitive and IM-resistant GISTs. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | The authors also provided preclinical evidence of the disease-specific impact of HDACi on KIT-positive GISTs, which has the potential to be translated into therapeutic activity . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | To overcome IM resistance in GIST patients, other drugs have been tested over the years, such as sorafenib, which displays clinical activity against TKI-resistant GISTs. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Heinrich and colleagues tested this compound in a panel of KIT- and PDGFRA-mutant kinases expressed by the transient transfection of the reference cell lines (GIST-T1/829 and IM-resistant GIST-T1). |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Sorafenib showed a good IC50 potency against all IM-resistant mutations, except those involving KIT codon 816 and PDGFRA codon 842 . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Among the available liposarcoma cell lines, LPS141 cells are valid candidates to test new anti-cancer drugs, while T449 and T778 are more suitable to study tumor progression and recurrence, as demonstrated by Stratford‘s team. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | A correlation between high proliferation rate and in vivo tumor-forming ability was also observed . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Simultaneously, cell lines derived from dedifferentiated liposarcomas carrying 12q13-15 region amplification (including MDM2 and CDK4 genes) represent an excellent preclinical model for the study of well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma development and proliferation. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | The p53 significance in both cancer development and therapy response has aroused interest in terms of the p53–MDM2 interaction as a possible target for small-molecule therapy over the years . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | MDM2 inhibition results in antitumor activity and increased apoptosis, as demonstrated by Müller and colleagues in an in vitro study conducted on WDLPS (T449 and T778) and DDLPS (FU-DDLS-1) TP53 wild-type and MDM2 amplified cell lines, indicating a potential link between treatment response and the mutational status of these genes . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Unfortunately, for some visceral sarcoma subtypes, very few cellular models are available, as in the case of AS . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Krump-Konvalinkova and Bittinger were able to establish the human endothelial AS-M cell line from a cutaneous angiosarcoma. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | These cells displayed endothelial characteristics, as CD31 expression, and might be considered a suitable model to investigate human endothelial cells . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Several studies have also been conducted to develop three-dimensional culture systems for sarcomas, with the aim of better resembling the surrounding extracellular matrix and overcoming the disadvantages of two-dimensional cell cultures. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Maintaining cells in a 2D culture results in morphological changes, leading to altered gene and protein expression and different cell behavior compared to the original tissue. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | 3D cellular models can overcome these limitations since the architecture of the original tissue and the native cell-cell and cell–extracellular matrix interactions are preserved . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | 3D cultures are also valuable tools for studying the microenvironment’s influence on cells within a tumor and their response to drug treatment . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | However, inducing sarcoma cell proliferation in a 3D culture system is more challenging than in a 2D culture. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | This can be explained by the impact of the microenvironment on sarcoma cell proliferation, including angiogenic capability, and by the presence of distinct cell–matrix adhesion molecules in 3D and 2D models . |
PMC10669128 | Preclinical Models of Visceral Sarcomas | As previously discussed, cells of a specific sarcoma subtype can differentiate into multiple lineages in vitro in the presence of certain inducing factors. |
PMC10669128 | Preclinical Models of Visceral Sarcomas | Thus, it is clear that not only the cell of origin but also the tumor microenvironment plays a crucial role in determining the final tumor phenotype . |
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